AIMS: To investigate the effects of lipid lowering therapy on the fraction unbound and dosage requirement of cyclosporine in heart transplant recipients. METHODS: Cyclosporine fraction unbound (fu) was measured ex vivo in plasma obtained from heart transplant recipients (n=12) before and after lipid lowering treatment, using equilibrium dialysis. Cyclosporine trough concentration data were also collected from cardiac transplant recipients (n=32) who received simvastatin for the treatment of hyperlipidaemia. Cyclosporine daily dosage and total concentration (monoclonal FPIA method) were recorded for periods up to 6 months before and after simvastatin administration. The total number of dose rate-concentration observations was 172 before and 135 after simvastatin administration respectively. Using a population pharmacokinetic approach (implemented in P-PHARM software) the ratio of dose rate to trough concentration at steady state (DR/C[SS trough]), an estimation of apparent clearance, was determined. The posterior Bayesian estimate of DR/C(SS trough) was calculated for each patient before and after simvastatin administration. RESULTS: The mean fu increased by 29%, from 1.40 +/- 0.1% (mean +/- s.d.) to 1.82 +/- 0.22% after simvastatin administration (P < 0.01). Mean trough concentrations of cyclosporine in whole blood were 349 microg l-1 before and 242 microg l-1 after simvastatin administration (P < 0.0001). The mean cyclosporine daily dosage was 2.87 mg kg-1 and 2.33 mg kg-1 (NS), before and after simvastatin administration respectively. The average cyclosporine DR/C(SS trough) was significantly increased from 24.5 l h-1 before to 28.9 l h-1 after simvastatin administration (P < 0.05). Furthermore the median increase in cyclosporine DR/C(SS trough) was 18 l h-1 (-3.1 to 42.1 l h-1, interquartile range). CONCLUSIONS: Cyclosporine fraction unbound and clearance are increased following co-administration of lipid lowering agents, necessitating closer monitoring of cyclosporine total blood concentration when lipid lowering agents are administered concomitantly with cyclosporine.
AIMS: To investigate the effects of lipid lowering therapy on the fraction unbound and dosage requirement of cyclosporine in heart transplant recipients. METHODS:Cyclosporine fraction unbound (fu) was measured ex vivo in plasma obtained from heart transplant recipients (n=12) before and after lipid lowering treatment, using equilibrium dialysis. Cyclosporine trough concentration data were also collected from cardiac transplant recipients (n=32) who received simvastatin for the treatment of hyperlipidaemia. Cyclosporine daily dosage and total concentration (monoclonal FPIA method) were recorded for periods up to 6 months before and after simvastatin administration. The total number of dose rate-concentration observations was 172 before and 135 after simvastatin administration respectively. Using a population pharmacokinetic approach (implemented in P-PHARM software) the ratio of dose rate to trough concentration at steady state (DR/C[SS trough]), an estimation of apparent clearance, was determined. The posterior Bayesian estimate of DR/C(SS trough) was calculated for each patient before and after simvastatin administration. RESULTS: The mean fu increased by 29%, from 1.40 +/- 0.1% (mean +/- s.d.) to 1.82 +/- 0.22% after simvastatin administration (P < 0.01). Mean trough concentrations of cyclosporine in whole blood were 349 microg l-1 before and 242 microg l-1 after simvastatin administration (P < 0.0001). The mean cyclosporine daily dosage was 2.87 mg kg-1 and 2.33 mg kg-1 (NS), before and after simvastatin administration respectively. The average cyclosporine DR/C(SS trough) was significantly increased from 24.5 l h-1 before to 28.9 l h-1 after simvastatin administration (P < 0.05). Furthermore the median increase in cyclosporine DR/C(SS trough) was 18 l h-1 (-3.1 to 42.1 l h-1, interquartile range). CONCLUSIONS:Cyclosporine fraction unbound and clearance are increased following co-administration of lipid lowering agents, necessitating closer monitoring of cyclosporine total blood concentration when lipid lowering agents are administered concomitantly with cyclosporine.
Authors: Hye Eun Yoon; Joon Chang Song; Bok Jin Hyoung; Hyeon Seok Hwang; So Young Lee; Youn Joo Jeon; Bum Soon Choi; Yong Soo Kim; Chul Woo Yang Journal: Korean J Intern Med Date: 2009-08-26 Impact factor: 3.165
Authors: Josephine L C Anderson; Markus van der Giet; Antonio W Gomes Neto; Stephan J L Bakker; Uwe J F Tietge Journal: Eur J Clin Invest Date: 2021-05-27 Impact factor: 4.686