Browsing by Author "Dashti-Khavidaki, Simin"

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    Clinical Pharmacokinetics of Oral Versus Sublingual Administration of Tacrolimus in Adult Liver Transplant Recipients
    (Başkent Üniversitesi, 2012-12) Nasiri-Toosi, Zahra; Khalili, Hossein; Sadrai, Sima; Abdollahi, Alireza; Irajian, Hamideh; Jafarian, Ali; Nasiri-Toosi, Mohsen; Dashti-Khavidaki, Simin
    Objectives: Oral tacrolimus administration is the common route of drug delivery. Recent studies suggest sublingual administration of tacrolimus as an alternative route may produce comparable drug trough levels with similar or even lower doses than the oral route, especially in lung transplant recipients; however, most of this research does not encompass intraindividual variations compared between the 2 routes. This study sought to compare the bioavailability and blood trough concentrations of orally and sublingually administered tacrolimus in adult liver transplant recipients by considering intraindividual variations in tacrolimus pharmacokinetics properties. Materials and Methods: Six adult liver transplant recipients received their tacrolimus either orally or sublingually within 2 consecutive days. Blood samples to determine tacrolimus concentrations were gathered at 0, 0.5, 1, 2, 4, 6, and 12 hours after oral and sublingual tacrolimus administration. Mean data values were used to calculate the pharmacokinetics parameters via the feathering or residual method, using the 1-compartment, first-order elimination pharmacokinetics model. Compared pharmacokinetics parameters included drug bioavailability, maximum blood concentration (Cmax), time to reach maximum blood level (Tmax), and trough blood concentrations. Results: Trough whole blood levels, area under the concentration-time curve, Tmax, and Cmax after oral and sublingual administration of tacrolimus were not significantly different (10.4 ± 7.4 vs 11.2 ± 11.3 ng/mL for trough blood concentration, 181.5 ± 114.1 vs 160.8 ± 115.9 ng.h/mL for AUC, 1.9 ± 1.2 vs 1.4 ± 0.7 h for Tmax, and 19.9 ± 10.8 vs 17.2 ± 11.7 ng/mL for Cmax). A double-peak phenomenon was observed in some concentration-time profiles. Conclusions: Sublingual tacrolimus administration does provide therapeutic drug concentrations in adult liver transplant recipients. Therefore, sublingual tacrolimus may confidently be considered as an alternative route to oral administration in patients who are unable to swallow their drugs.