British Journal of Clinical Pharmacology, Apr 11, 2011
From a list of 216 candidate drugs (349 CYP-perpetrator pairs, CYP-PPs), 36 inhibitors and eight ... more From a list of 216 candidate drugs (349 CYP-perpetrator pairs, CYP-PPs), 36 inhibitors and eight inducers were accepted as major perpetrators of PK-DDIs, resulting in 58 CYP-PPs. In comparison, the clinical version of the CDIT had a sensitivity of 33% and a positive predictive value of 68%. One hundred and ninety-nine CYP-PPs were rejected as major perpetrators, and 92 CYP-PPs had insufficient published human pharmacokinetic data for robust classification. CONCLUSIONS Using a criteria-based assessment, the number of drugs that are proven or likely major perpetrators of CYP-mediated PK-DDIs is relatively small. Current clinical decision support on PK-DDIs is inconsistent with the published evidence and can be improved using simple criteria.
Background: Understanding the performance of prescribed medications in day-today practice is impo... more Background: Understanding the performance of prescribed medications in day-today practice is important to minimize harm, maximize clinical benefits, and, eventually, better target the people who are most likely to benefit, especially in hospice/palliative care where there may be limited time to optimize prescribing. Metoclopramide, a benzamide prokinetic antiemetic, is widely used for a number of indications including nausea, vomiting, hiccups, and reflux. It has recently had a new ''black box'' warning issued by the Food and Drug Administration in relation to tardive dyskinesia to limit use to 12 weeks. Methods: A consecutive cohort of patients from 12 participating centers in two countries who were having metoclopramide initiated had data collected at three time points-baseline, 2 days (clinical benefit), and day 7 (clinical harm). Additionally, harms could be recorded at any time. Results: Of the 53 people included in the cohort, 23 (43%) reported benefit at 48 hours, but only 18 (34%) of these people were still using it one week after commencing it. For the other 5, the medication was ceased due to harms. The most frequent harms were akathisia (n = 4), headache (n = 4), and abdominal pain (n = 4). Nine people (17%) had no clinical benefit and experienced harms. Conclusion: Overall, one in three people gained net clinical benefit at one week. Limiting effects include sideeffects that need to be sought actively in clinical care.
Renal disease alters the effects of many drugs, particularly when active drug moieties are renall... more Renal disease alters the effects of many drugs, particularly when active drug moieties are renally cleared. Drug doses should usually be reduced in renal disease in proportion to the predicted reduction in clearance of the active drug moiety. Patient factors to consider in adjusting drug doses include the degree of renal impairment and patient size. Drug factors to consider in adjusting doses include the fraction of the drug excreted unchanged in urine and the drug's therapeutic index. Estimates of renal function are useful to guide dosing of renally cleared drugs with medium therapeutic indices, but are not precise enough to guide dosing of drugs with narrow therapeutic indices. This article discusses principles of drug dose adjustment in renal disease.
The recent report that clopidogrel efficacy may be more dependent on paraoxonase-1 (PON1) than on... more The recent report that clopidogrel efficacy may be more dependent on paraoxonase-1 (PON1) than on cytochrome P450 2C19 (CYP2C19) activity raises questions about the roles of these and other enzymes in clopidogrel activation. To provide insight into the emerging PON1 versus CYP2C19 debate, this commentary summarizes the clinical evidence on the pharmacokinetic determinants of clopidogrel efficacy. We then review the in vitro studies investigating the enzymes involved in clopidogrel activation, and comment on their strengths and limitations. There is agreement amongst in vitro studies regarding the involvement of CYP1A2 and CYP2B6 in the metabolism of clopidogrel to 2-oxo-clopidogrel. However, the evidence for other CYP enzymes in the first activation step (e.g. CYP2C19 and CYP3A4) is inconsistent and dependent on the in vitro test system and laboratory. All major drug metabolizing CYP enzymes are capable of converting 2-oxo-clopidogrel to sulfenic acid intermediates that subsequently form the active thiol metabolite. However, the extent of CYP involvement in this second step has been challenged, and new evidence suggests that CYP-independent hydrolytic cleavage of the thioester bond may be more important than oxidative metabolism.
e17 the risk was greater (HR 2.23, 95% confidence interval 1.17-4.24, P= 0.015). Conclusions: It ... more e17 the risk was greater (HR 2.23, 95% confidence interval 1.17-4.24, P= 0.015). Conclusions: It is possible to demonstrate the impact of CYP2C19 genotype on clopidogrel efficacy using a purely record linkage approach. Furthermore, this association appears to be particularly strong following ischaemic stroke where particularly in the UK clopidogrel monotherapy is usually used.
With the increasing prevalence of type 2 diabetes mellitus (T2DM) in women of childbearing age, p... more With the increasing prevalence of type 2 diabetes mellitus (T2DM) in women of childbearing age, prescribing antidiabetic medications in first-trimester pregnancy is becoming more common. Metformin treatment during this time is usually avoided in countries with well-resourced healthcare. This is based on historical concerns about safety to the foetus and the widespread availability of insulin. However, there is now increasing interest in the potential benefits of metformin in pregnant women with T2DM. In this commentary, the main evidence supporting metformin safety in pregnancy is summarized, with an emphasis on the first trimester. Based on a structured literature search, the recent randomized controlled trials comparing metformin and insulin are reviewed. We then show that prescribing advice for metformin in pregnancy is inconsistent and product information/package inserts (PI) are universally out of date. This causes confusion and pushes some women and their clinicians to change from metformin to insulin. The potential advantages of metformin in pregnant women with T2DM are then discussed, including oral dosing and improved acceptability, lower resource utilization and cost, decreased insulin requirements, less maternal weight gain and less risk of maternal and neonatal hypoglycaemia. The conclusion is that metformin is a cheap and efficacious antidiabetic medication for many pregnant women with T2DM, with reasonable evidence for safety. Drug information resources should be updated so that metformin can be considered more broadly in women with T2DM who present for antenatal care.
Aims To determine the milk-to-plasma (M/P) concentration ratio of celecoxib, and estimate likely ... more Aims To determine the milk-to-plasma (M/P) concentration ratio of celecoxib, and estimate likely infant exposure. Methods Blood and milk were sampled for 48 h after oral administration of celecoxib 200 mg to six lactating volunteers. The M/P ratio was derived from the area under the concentration-time curves (0-∞) and the infant 'dose' estimated from celecoxib concentrations in milk. Results The median (range) M/P ratio was 0.18 (0.15-0.26). The median (range) infant 'dose' was 0.23% (0.17-0.30%) of the maternal dose, adjusted for weight. Conclusion The relative 'dose' of celecoxib to which infants are exposed via milk is very low, suggesting that breastfeeding during routine dosing would pose minimal risk.
Warfarin and the new oral anticoagulants are licensed for non-valvular atrial fibrillation and ve... more Warfarin and the new oral anticoagulants are licensed for non-valvular atrial fibrillation and venous thromboembolism. The choice of anticoagulant depends on the characteristics of the patient and the medicine. Key considerations include patient adherence, kidney and liver function, and potential interactions with concomitant drugs. Dosing should accommodate these factors. Patients should be regularly monitored for bleeding, adherence to treatment, and changing comorbidities and concomitant drugs. Renal function should be checked at least annually. Other than idarucizumab for dabigatran, there are no widely available antidotes for the new oral anticoagulants. In a patient with normal renal and hepatic function, drug concentrations and anticoagulant effect are expected to diminish by over 90% after stopping treatment for 48 hours. Matching the characteristics of the individual patient to the characteristics of each oral anticoagulant is important when choosing therapy. 4 The Table lists approved indications and key characteristics of oral anticoagulants. A major difference between NOACs is the contribution of the kidneys to drug clearance, which is greatest for dabigatran. Key decision points when choosing an oral anticoagulant are illustrated in the Figure. Patient characteristics Warfarin should be used for patients with mechanical heart valves as data for the NOACs are either lacking or show inferiority to warfarin. We recommend that patients established on warfarin with a high percentage of time in the therapeutic range (e.g. >70% of INR values at target) 5 should remain on warfarin. The uncertainty around dosing of NOACs in severe liver impairment (e.g. Child Pugh C) or renal impairment (e.g. creatinine clearance <30 mL/min) means that warfarin is favoured in these patients. NOACs are not recommended during pregnancy or breastfeeding as there are alternatives associated with greater safety and efficacy data. Warfarin is teratogenic and thus contraindicated during pregnancy, but is compatible with breastfeeding as transfer into breastmilk is negligible. Drug-drug interactions Co-administration of medicines that are strong enzyme or transporter inducers (e.g. rifampicin) or inhibitors (e.g. erythromycin) 6 are expected to
SGLT2 are responsible for glucose reabsorption in the proximal tubules of the kidneys (Fig. 1). 2... more SGLT2 are responsible for glucose reabsorption in the proximal tubules of the kidneys (Fig. 1). 2 SGLT2 is a low-affinity, high capacity glucose transporter located in segment 1 of the proximal tubule (in the apical membrane of the tubule cells). Under normal circumstances SGLT2 reabsorbs about 90% of the filtered glucose (Fig. 2). SGLT2 is minimally expressed in other tissues. 3 Pharmacology of SGLT2 inhibitors The first two SGLT2 inhibitors approved in Australia, dapagliflozin and canagliflozin, have high bioavailability. They have a half-life of about 12 hours and are taken once a day. Dapagliflozin can be taken with or without food, while it is recommended that canagliflozin is taken before the first meal of the day. Both drugs are highly protein bound in plasma and are metabolised in the liver via glucuronidation.
Changes in inpatient medicine prescribing during COVID‐19 lockdown
Internal Medicine Journal
BackgroundNew Zealand went into lockdown March 2020 successfully eliminating the circulation of t... more BackgroundNew Zealand went into lockdown March 2020 successfully eliminating the circulation of the coronavirus disease 2019 (COVID‐19) virus. During lockdown there were reduced rates of respiratory infections and hospital admission numbers were low. At the time, rumours of benefit and harm of medicines for COVID‐19 were widespread in the lay and medical media.AimTo describe changes in inpatient prescribing in an acute general medicine service during the New Zealand COVID‐19 lockdown in 2020.MethodsRates of prescribing of medicines during the 33 days of lockdown were compared with a 33‐day control period before lockdown. Prescriptions, patients and bed days were calculated from the hospital patient administration and electronic prescribing and administration systems.ResultsIn the general medicine service, acute admissions were 20% lower during lockdown (from 1216 pre‐lockdown to 974). There was a small decrease in the rate of prescriptions per patient (10.1 vs 10.4, P = 0.01) during...
Paracentesis for cancer-related ascites in palliative care: An international, prospective cohort study
Palliative Medicine
Background: Paracentesis is commonly undertaken in patients with cancer-related ascites. Aim: To ... more Background: Paracentesis is commonly undertaken in patients with cancer-related ascites. Aim: To systematically investigate the symptomatic benefits and harms experienced by patients with cancer undergoing paracentesis using real-world data in the palliative care setting. Design: Prospective, multisite, observational, consecutive cohort study. Benefits and harms of paracentesis were assessed between 01/07/2018 and 31/02/2021 as part of routine clinical assessments by treating clinicians at four timepoints: (T0) before paracentesis; (T1) once drainage ceased; (T2) 24 h after T1 and (T3) 28 days after T1 or next paracentesis, if sooner. Setting/participants: Data were collected from 11 participating sites across five countries (Australia, England, Hong Kong, Malaysia and New Zealand) on 111 patients undergoing paracentesis via a temporary (73%) or indwelling (21%) catheter: 51% male, median age 69 years, Australia-modified Karnofsky Performance Score 50. Results: At T1 ( n = 100), sym...
thiazide diuretics alter the pharmacokinetics of metformin in patients with type 2 diabetes alrea... more thiazide diuretics alter the pharmacokinetics of metformin in patients with type 2 diabetes already established on metformin?
AIMS To assess a persuasive multimodel approach to decreasing unnecessary intravenous (IV) clarit... more AIMS To assess a persuasive multimodel approach to decreasing unnecessary intravenous (IV) clarithromycin use for community-acquired pneumonia (CAP) in Canterbury District Health Board (CDHB) hospitals. METHODS In December 2013, CDHB guidelines for empiric treatment of CAP changed to prioritise oral azithromycin over IV clarithromycin. The multimodel approach we used to implement this change included obtaining stakeholder agreement, improved guidelines access, education and pharmacist support. The impact of the intervention was evaluated by comparing macrolide usage and expenditure for the four years pre- and post-intervention. RESULTS Mean annual clarithromycin IV use decreased by 72% from 6.4 to 1.8 defined daily doses (DDDs) per 1,000 occupied bed days (OBDs) post-intervention, while oral azithromycin increased by 833% (4.2 to 39.2 DDDs per 1,000 OBDs). Concurrently, oral clarithromycin use decreased by 91% (32.9 to 2.9 DDDs per 1,000 OBDs), and roxithromycin by 71% (17.0 to 5.0 ...
Individual response to chemotherapy in patients with breast cancer is variable. Obesity and exerc... more Individual response to chemotherapy in patients with breast cancer is variable. Obesity and exercise are associated with better and worse outcomes, respectively, and it is known that both impact the systemic cytokine milieu. Cytochrome P450 (CYP) enzymes are responsible for the metabolism of many chemotherapy agents, and CYP enzyme activity has been shown to be modified by inflammatory cytokines in vitro and in vivo. Cytokine-associated changes in CYP metabolism may alter chemotherapy exposure, potentially affecting treatment response and patient survival. Therefore, better understanding of these biological relationships is required. This exploratory single arm open label trial investigated changes in in vivo CYP activity in twelve women treated for stage II or III breast cancer, and demonstrated for the first time the feasibility and safety of utilising the Inje phenotyping cocktail to measure CYP activity in cancer patients receiving chemotherapy. Relative CYP activity varied betw...
British Journal of Clinical Pharmacology, Apr 11, 2011
From a list of 216 candidate drugs (349 CYP-perpetrator pairs, CYP-PPs), 36 inhibitors and eight ... more From a list of 216 candidate drugs (349 CYP-perpetrator pairs, CYP-PPs), 36 inhibitors and eight inducers were accepted as major perpetrators of PK-DDIs, resulting in 58 CYP-PPs. In comparison, the clinical version of the CDIT had a sensitivity of 33% and a positive predictive value of 68%. One hundred and ninety-nine CYP-PPs were rejected as major perpetrators, and 92 CYP-PPs had insufficient published human pharmacokinetic data for robust classification. CONCLUSIONS Using a criteria-based assessment, the number of drugs that are proven or likely major perpetrators of CYP-mediated PK-DDIs is relatively small. Current clinical decision support on PK-DDIs is inconsistent with the published evidence and can be improved using simple criteria.
Background: Understanding the performance of prescribed medications in day-today practice is impo... more Background: Understanding the performance of prescribed medications in day-today practice is important to minimize harm, maximize clinical benefits, and, eventually, better target the people who are most likely to benefit, especially in hospice/palliative care where there may be limited time to optimize prescribing. Metoclopramide, a benzamide prokinetic antiemetic, is widely used for a number of indications including nausea, vomiting, hiccups, and reflux. It has recently had a new ''black box'' warning issued by the Food and Drug Administration in relation to tardive dyskinesia to limit use to 12 weeks. Methods: A consecutive cohort of patients from 12 participating centers in two countries who were having metoclopramide initiated had data collected at three time points-baseline, 2 days (clinical benefit), and day 7 (clinical harm). Additionally, harms could be recorded at any time. Results: Of the 53 people included in the cohort, 23 (43%) reported benefit at 48 hours, but only 18 (34%) of these people were still using it one week after commencing it. For the other 5, the medication was ceased due to harms. The most frequent harms were akathisia (n = 4), headache (n = 4), and abdominal pain (n = 4). Nine people (17%) had no clinical benefit and experienced harms. Conclusion: Overall, one in three people gained net clinical benefit at one week. Limiting effects include sideeffects that need to be sought actively in clinical care.
Renal disease alters the effects of many drugs, particularly when active drug moieties are renall... more Renal disease alters the effects of many drugs, particularly when active drug moieties are renally cleared. Drug doses should usually be reduced in renal disease in proportion to the predicted reduction in clearance of the active drug moiety. Patient factors to consider in adjusting drug doses include the degree of renal impairment and patient size. Drug factors to consider in adjusting doses include the fraction of the drug excreted unchanged in urine and the drug's therapeutic index. Estimates of renal function are useful to guide dosing of renally cleared drugs with medium therapeutic indices, but are not precise enough to guide dosing of drugs with narrow therapeutic indices. This article discusses principles of drug dose adjustment in renal disease.
The recent report that clopidogrel efficacy may be more dependent on paraoxonase-1 (PON1) than on... more The recent report that clopidogrel efficacy may be more dependent on paraoxonase-1 (PON1) than on cytochrome P450 2C19 (CYP2C19) activity raises questions about the roles of these and other enzymes in clopidogrel activation. To provide insight into the emerging PON1 versus CYP2C19 debate, this commentary summarizes the clinical evidence on the pharmacokinetic determinants of clopidogrel efficacy. We then review the in vitro studies investigating the enzymes involved in clopidogrel activation, and comment on their strengths and limitations. There is agreement amongst in vitro studies regarding the involvement of CYP1A2 and CYP2B6 in the metabolism of clopidogrel to 2-oxo-clopidogrel. However, the evidence for other CYP enzymes in the first activation step (e.g. CYP2C19 and CYP3A4) is inconsistent and dependent on the in vitro test system and laboratory. All major drug metabolizing CYP enzymes are capable of converting 2-oxo-clopidogrel to sulfenic acid intermediates that subsequently form the active thiol metabolite. However, the extent of CYP involvement in this second step has been challenged, and new evidence suggests that CYP-independent hydrolytic cleavage of the thioester bond may be more important than oxidative metabolism.
e17 the risk was greater (HR 2.23, 95% confidence interval 1.17-4.24, P= 0.015). Conclusions: It ... more e17 the risk was greater (HR 2.23, 95% confidence interval 1.17-4.24, P= 0.015). Conclusions: It is possible to demonstrate the impact of CYP2C19 genotype on clopidogrel efficacy using a purely record linkage approach. Furthermore, this association appears to be particularly strong following ischaemic stroke where particularly in the UK clopidogrel monotherapy is usually used.
With the increasing prevalence of type 2 diabetes mellitus (T2DM) in women of childbearing age, p... more With the increasing prevalence of type 2 diabetes mellitus (T2DM) in women of childbearing age, prescribing antidiabetic medications in first-trimester pregnancy is becoming more common. Metformin treatment during this time is usually avoided in countries with well-resourced healthcare. This is based on historical concerns about safety to the foetus and the widespread availability of insulin. However, there is now increasing interest in the potential benefits of metformin in pregnant women with T2DM. In this commentary, the main evidence supporting metformin safety in pregnancy is summarized, with an emphasis on the first trimester. Based on a structured literature search, the recent randomized controlled trials comparing metformin and insulin are reviewed. We then show that prescribing advice for metformin in pregnancy is inconsistent and product information/package inserts (PI) are universally out of date. This causes confusion and pushes some women and their clinicians to change from metformin to insulin. The potential advantages of metformin in pregnant women with T2DM are then discussed, including oral dosing and improved acceptability, lower resource utilization and cost, decreased insulin requirements, less maternal weight gain and less risk of maternal and neonatal hypoglycaemia. The conclusion is that metformin is a cheap and efficacious antidiabetic medication for many pregnant women with T2DM, with reasonable evidence for safety. Drug information resources should be updated so that metformin can be considered more broadly in women with T2DM who present for antenatal care.
Aims To determine the milk-to-plasma (M/P) concentration ratio of celecoxib, and estimate likely ... more Aims To determine the milk-to-plasma (M/P) concentration ratio of celecoxib, and estimate likely infant exposure. Methods Blood and milk were sampled for 48 h after oral administration of celecoxib 200 mg to six lactating volunteers. The M/P ratio was derived from the area under the concentration-time curves (0-∞) and the infant 'dose' estimated from celecoxib concentrations in milk. Results The median (range) M/P ratio was 0.18 (0.15-0.26). The median (range) infant 'dose' was 0.23% (0.17-0.30%) of the maternal dose, adjusted for weight. Conclusion The relative 'dose' of celecoxib to which infants are exposed via milk is very low, suggesting that breastfeeding during routine dosing would pose minimal risk.
Warfarin and the new oral anticoagulants are licensed for non-valvular atrial fibrillation and ve... more Warfarin and the new oral anticoagulants are licensed for non-valvular atrial fibrillation and venous thromboembolism. The choice of anticoagulant depends on the characteristics of the patient and the medicine. Key considerations include patient adherence, kidney and liver function, and potential interactions with concomitant drugs. Dosing should accommodate these factors. Patients should be regularly monitored for bleeding, adherence to treatment, and changing comorbidities and concomitant drugs. Renal function should be checked at least annually. Other than idarucizumab for dabigatran, there are no widely available antidotes for the new oral anticoagulants. In a patient with normal renal and hepatic function, drug concentrations and anticoagulant effect are expected to diminish by over 90% after stopping treatment for 48 hours. Matching the characteristics of the individual patient to the characteristics of each oral anticoagulant is important when choosing therapy. 4 The Table lists approved indications and key characteristics of oral anticoagulants. A major difference between NOACs is the contribution of the kidneys to drug clearance, which is greatest for dabigatran. Key decision points when choosing an oral anticoagulant are illustrated in the Figure. Patient characteristics Warfarin should be used for patients with mechanical heart valves as data for the NOACs are either lacking or show inferiority to warfarin. We recommend that patients established on warfarin with a high percentage of time in the therapeutic range (e.g. >70% of INR values at target) 5 should remain on warfarin. The uncertainty around dosing of NOACs in severe liver impairment (e.g. Child Pugh C) or renal impairment (e.g. creatinine clearance <30 mL/min) means that warfarin is favoured in these patients. NOACs are not recommended during pregnancy or breastfeeding as there are alternatives associated with greater safety and efficacy data. Warfarin is teratogenic and thus contraindicated during pregnancy, but is compatible with breastfeeding as transfer into breastmilk is negligible. Drug-drug interactions Co-administration of medicines that are strong enzyme or transporter inducers (e.g. rifampicin) or inhibitors (e.g. erythromycin) 6 are expected to
SGLT2 are responsible for glucose reabsorption in the proximal tubules of the kidneys (Fig. 1). 2... more SGLT2 are responsible for glucose reabsorption in the proximal tubules of the kidneys (Fig. 1). 2 SGLT2 is a low-affinity, high capacity glucose transporter located in segment 1 of the proximal tubule (in the apical membrane of the tubule cells). Under normal circumstances SGLT2 reabsorbs about 90% of the filtered glucose (Fig. 2). SGLT2 is minimally expressed in other tissues. 3 Pharmacology of SGLT2 inhibitors The first two SGLT2 inhibitors approved in Australia, dapagliflozin and canagliflozin, have high bioavailability. They have a half-life of about 12 hours and are taken once a day. Dapagliflozin can be taken with or without food, while it is recommended that canagliflozin is taken before the first meal of the day. Both drugs are highly protein bound in plasma and are metabolised in the liver via glucuronidation.
Changes in inpatient medicine prescribing during COVID‐19 lockdown
Internal Medicine Journal
BackgroundNew Zealand went into lockdown March 2020 successfully eliminating the circulation of t... more BackgroundNew Zealand went into lockdown March 2020 successfully eliminating the circulation of the coronavirus disease 2019 (COVID‐19) virus. During lockdown there were reduced rates of respiratory infections and hospital admission numbers were low. At the time, rumours of benefit and harm of medicines for COVID‐19 were widespread in the lay and medical media.AimTo describe changes in inpatient prescribing in an acute general medicine service during the New Zealand COVID‐19 lockdown in 2020.MethodsRates of prescribing of medicines during the 33 days of lockdown were compared with a 33‐day control period before lockdown. Prescriptions, patients and bed days were calculated from the hospital patient administration and electronic prescribing and administration systems.ResultsIn the general medicine service, acute admissions were 20% lower during lockdown (from 1216 pre‐lockdown to 974). There was a small decrease in the rate of prescriptions per patient (10.1 vs 10.4, P = 0.01) during...
Paracentesis for cancer-related ascites in palliative care: An international, prospective cohort study
Palliative Medicine
Background: Paracentesis is commonly undertaken in patients with cancer-related ascites. Aim: To ... more Background: Paracentesis is commonly undertaken in patients with cancer-related ascites. Aim: To systematically investigate the symptomatic benefits and harms experienced by patients with cancer undergoing paracentesis using real-world data in the palliative care setting. Design: Prospective, multisite, observational, consecutive cohort study. Benefits and harms of paracentesis were assessed between 01/07/2018 and 31/02/2021 as part of routine clinical assessments by treating clinicians at four timepoints: (T0) before paracentesis; (T1) once drainage ceased; (T2) 24 h after T1 and (T3) 28 days after T1 or next paracentesis, if sooner. Setting/participants: Data were collected from 11 participating sites across five countries (Australia, England, Hong Kong, Malaysia and New Zealand) on 111 patients undergoing paracentesis via a temporary (73%) or indwelling (21%) catheter: 51% male, median age 69 years, Australia-modified Karnofsky Performance Score 50. Results: At T1 ( n = 100), sym...
thiazide diuretics alter the pharmacokinetics of metformin in patients with type 2 diabetes alrea... more thiazide diuretics alter the pharmacokinetics of metformin in patients with type 2 diabetes already established on metformin?
AIMS To assess a persuasive multimodel approach to decreasing unnecessary intravenous (IV) clarit... more AIMS To assess a persuasive multimodel approach to decreasing unnecessary intravenous (IV) clarithromycin use for community-acquired pneumonia (CAP) in Canterbury District Health Board (CDHB) hospitals. METHODS In December 2013, CDHB guidelines for empiric treatment of CAP changed to prioritise oral azithromycin over IV clarithromycin. The multimodel approach we used to implement this change included obtaining stakeholder agreement, improved guidelines access, education and pharmacist support. The impact of the intervention was evaluated by comparing macrolide usage and expenditure for the four years pre- and post-intervention. RESULTS Mean annual clarithromycin IV use decreased by 72% from 6.4 to 1.8 defined daily doses (DDDs) per 1,000 occupied bed days (OBDs) post-intervention, while oral azithromycin increased by 833% (4.2 to 39.2 DDDs per 1,000 OBDs). Concurrently, oral clarithromycin use decreased by 91% (32.9 to 2.9 DDDs per 1,000 OBDs), and roxithromycin by 71% (17.0 to 5.0 ...
Individual response to chemotherapy in patients with breast cancer is variable. Obesity and exerc... more Individual response to chemotherapy in patients with breast cancer is variable. Obesity and exercise are associated with better and worse outcomes, respectively, and it is known that both impact the systemic cytokine milieu. Cytochrome P450 (CYP) enzymes are responsible for the metabolism of many chemotherapy agents, and CYP enzyme activity has been shown to be modified by inflammatory cytokines in vitro and in vivo. Cytokine-associated changes in CYP metabolism may alter chemotherapy exposure, potentially affecting treatment response and patient survival. Therefore, better understanding of these biological relationships is required. This exploratory single arm open label trial investigated changes in in vivo CYP activity in twelve women treated for stage II or III breast cancer, and demonstrated for the first time the feasibility and safety of utilising the Inje phenotyping cocktail to measure CYP activity in cancer patients receiving chemotherapy. Relative CYP activity varied betw...
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Papers by Matthew Doogue