C SCUDERI 1,2, JAHAN S1, PARKER S3, WALLIS S3, JACKS M1, JOHN G1, MCWHINNEY B4, UNGERER J4, MALLETT A6,7,9,10, HEALY H1,7, ROBERTS J3,5,6,9, STAATZ C2
1Qld Health MNHHS Kidney Health Service, Brisbane, Australia, 2School of Pharmacy, The University of Queensland, Brisbane, Australia, 3UQ Centre for Clinical Research, Faculty of Medicine, Brisbane, Australia, 4Pathology Queensland, Brisbane, Royal Brisbane & Women’s Hospital, Brisbane, Australia, 5Division of Anaesthesiology Critical Care Emergency and Pain Medicine, , France, 6Faculty of Medicine, The University of Queensland, Brisbane, Australia, 7Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia, 8Department of Pharmacy, Royal Brisbane & Women’s Hospital, Brisbane, Brisbane, Australia, 9Department of Renal Medicine, Townsville University Hospital, Townsville, Australia, 10College of Medicine and Dentistry, James Cook University, Townsville, Australia
Aim: A prospective, observational study was conducted to characterise the pharmacokinetics of trimethoprim-sulfamethoxazole in adult kidney transplant patients during its use for PJP prophylaxis.
Methods: Pharmacokinetic profiling was performed in 19 adult, kidney transplant patients prescribed 80mg/400mg prophylactic dose of trimethoprim-sulfamethoxazole respectively for at least 10 weeks. Serial blood samples were taken pre-dose (0) and 0.5, 1, 2, 4 and 8-hours post-dose on a single occasion for measurement in plasma using high performance liquid chromatography. Trimethoprim-sulfamethoxazole minimum concentration (Cmin), maximum concentration (Cmax), and area-under-the concentration-time-curve from 0 to 8 hours post-dose (AUC0-8) were estimated using the trapezoidal method.
Background: Pneumocystis jiroveci pneumonia (PJP) is a potentially life-threatening opportunistic infection seen in immunosuppressed patients. Effective prophylaxis of PJP is essential with the drug combination trimethoprim-sulfamethoxazole currently used as first-line therapy in kidney transplant patients. Little is known about the pharmacokinetics of trimethoprim-sulfamethoxazole in this cohort and whether there is any association between drug exposure and patient outcomes.
Results: Large variation in drug exposure was evident. Mean (±SD) trimethoprim Cmin was 0.4 (+/- 0.3) mg/L and Cmax was 1.1 mg/L (+/- 0.54) mg/L. Mean (±SD) sulfamethoxazole Cmin was 8.58 (+/- 4.5) mg/L and mean Cmax concentration was 26 mg/L (+/- 8.3mg/L). The mean AUC0-8 for trimethoprim was 6.7 mg.hr/L (range 2.1 -18.7 mg/L) and sulfamethoxazole was 148.6 mg/L (range 52.8-209.2mg.hr/L). Large between-subject pharmacokinetic variability was evident with a 4 -fold difference in AUC0-8 across the cohort.
Conclusions: Our findings suggest a considerable variation in patient blood concentrations which warrants further investigation into optimising treatment based on patient outcomes in relation to PJP prophylaxis and other infections that can be treated with trimethoprim-sulfamethoxazole.
Carla Scuderi is the Pharmacist Team Leader for the Kidney Health Service based at Royal Brisbane and Women’s hospital and is also a course coordinator in the University of Queensland Post graduate Clinical Pharmacy Program. Carla has previously been a community pharmacy manager and owner and quality use of medicines facilitator. Carla’s is undertaking a PhD investigating immunosuppressant microsampling and the pharmacist’s role in kidney transplant patient care. Carla’s other research interests include kidney supportive care and pharmacist interventions.