Effects of Simvastatin in Hyperlipidemic Renal Transplant Patients Receiving Cyclosporine

Rehman, Mohammed A.; Al-Sulaiman, M. H.; Mousa, Dujanah; Al-Hawas, Fahad; Abdalla, Abdalla H.; Rassoul, Zalmai; Al-Khader, Abdullah A

doi:10.1097/00007890-199508270-00018

Cited by 18 publications

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“…Total concentration of cyclosporine in whole blood is Lipid lowering therapy is commonly administered to post transplant patients to overcome hyperlipidaemia and to routinely monitored following transplantation while routine measurement of unbound cyclosporine is restricted owing prevent coronary artery disease [8][9][10]. The HMG-CoA reductase inhibitors, including simvastatin, are among the to the complexity of methods.…”

Section: Patients ( Paired T-test P<005)mentioning

confidence: 99%

“…Lipid lowering therapy is commonly used in this patient group to treat hypercholesterIn these studies [13,14,15] cyclosporine unbound fraction was not measured. It was proposed however that hyperlipidaolaemia in which HMG-CoA reductase inhibitors such as simvastatin [8,9] or pravastatin [10] are the most commonly emia may decrease cyclosporine clearance by reducing the cyclosporine fraction unbound in plasma, and conversely the administration of lipid lowering agents may alter the fraction…”

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confidence: 99%

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Effect of simvastatin on cyclosporine unbound fraction and apparent blood clearance in heart transplant recipients

Akhlaghi

McLachlan

Keogh

et al. 1997

Brit J Clinical Pharma

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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/Csstrough ), an estimation of apparent clearance, was determined. The posterior Bayesian estimate of DR/Csstrough 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 μg l−1 before and 242 μg 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/Csstrough 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/Csstrough 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.

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Section: Patients ( Paired T-test P<005)mentioning

confidence: 99%

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confidence: 99%