Objectives: To study the effect of concomitant administering of pomegranate juice orally (PJ) on bioavailability of cyclosporine A (CsA) and independently its potential nephroprotective effect against CsA induced nephrotoxicity. Methods: A- Pharmacokinetic study (PK), Wister rats were divided into groups (each 6 rats) I-: CsA PO + Vehicle; II- CsA IP + Vehicle, III- CsA PO + PJ, IV- CsA IP + PJ. CsA dose was 20 mg/kg for 5 days the vehicle or PJ (2 ml) was given 1 h before drug administration. Blood samples were taken at the 1st and 5th day at specified times and CsA level was determined by immune assays. Relative bioavailability of CsA was determined. B- Nephroprotection study (separate study to administer bioequivalent CsA PO doses, in view of PK study), I- ( CsA 13 mg PO + 2 ml PJ .II- CsA 20 mg P0 + 2 ml vehicle (for 28 day). The design also includes two control groups (vehicle alone or PJ alone). Blood samples for drug analysis, biochemical investigations and kidney samples for histopathology were taken at the 28th day. Results: PJ juice enhanced the bioavailability of oral CsA by about 50% (P > 0.05). But CsA (IP) was not affected after repeated administration for 5 days. Independently, the marked kidney damage induced by CsA was reversed by concomitant administration of PJ as well as it attenuated the increase in serum creatinine. Conclusions: Repeated administration of pomegranate juice enhance CsA oral bioavailability which likely due to inhibition of intestinal enzymes and transport pump. Independently it caused significant attenuation of CsA induced renal toxicity.
Background: Tacrolimus is immunosuppressive agent used for the prevention of rejection in kidney transplant patients, has narrow therapeutic range, and variable pharmacokinetics. Objectives: To identify the optimum Tacrolimus blood trough level for Saudi kidney transplant patients (SKTP). Method: The research population consisted of 100 SKTP at the Armed Forces Hospital in the Southern Region (AFHSR) treated with Tacrolimus and followed-up for a period of 24 months (2012 till 2014). Results: A significant relationship between Tacrolimus trough level and incidence of kidney rejection was remarkably found only after 180 days post-transplantation. During this period, Tacrolimus mean trough level (ng/ml) was 7.4 ± 0.2 in SKTP with no rejection, 5.3 ± 0.7 for those with acute rejection, and 3.8 ± 0.4 for those with chronic rejection. Furthermore, the coefficient of variation (CV%) which reflects fluctuation in Tacrolimus trough level, was obviously high in SKTP with acute rejection in all post-kidney-transplant periods. Conclusion: After 6 month post-kidney transplantation in SKTP, Tacrolimus trough level (<5 ng/ml can lead to graft loss, great fluctuation in its level is a major risk factor in incidence of rejection. Further research at genetic level is needed to guide optimal dosing in the early period post transplantation.
Tacrolimus (Fk506)-based immunosuppressant regimen has become the cornerstone in managing kidney transplant patients (KTP) , where it has been used typically used on chronic basis. However, various adverse effects on multiple organ systems are expected and their incidence is depending on many variables including genetic and non-genetic factors. The present study aims to explore the adverse effects associated with the chronic use of Tacrolimus -based immunosuppressant regimen in Saudi kidney transplant patients (SKTP). It was performed retrospectively at Kidney
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