Gastric Emptying Time in Renal Transplant Recipients Treated with Cyclosporine

Abstract

Gastric emptying time (GET) appears to be a rate-limiting factor in the absorption of cyclosporine-A (CsA) and may be responsible for intra- and interpatient variability of CsA bioavailability. Few studies have assessed gastric motility after renal transplantation. The purpose of this study was to evaluate gastric emptying of semi-solid material in stable renal transplant patients with reference to blood CsA levels. The GET of semi-solids (GET t <inf>1/2</inf>, half emptying time) was measured in 16 transplant recipients who were taking CsA (Neoral), prednisolone and azathioprine (or mycophenolate mofetil). The GET (t<inf>1/2</inf>) measured by radionuclide methods, was analyzed with reference to the daily CsA doses, levels of CsA (C<inf>0</inf>), and serum creatinine concentrations. The mean GET (t<inf>1/2</inf>) was 89.1 ± 26.4 minutes. Twelve patients exhibited delayed gastric emptying with a mean CsA level of 171.8 ± 56 ng/mL and a mean dose of 4.1 ± 1.1 mg/kg/d. The GET (t<inf>1/2</inf>) was not significantly correlated with the serum creatinine levels, the time since transplantation, or the CsA concentration. In addition, the correlation between the mean daily CsA dose and the GET (t<inf>1/2</inf>) was only weakly positive, (r = .33, P = .2) and therefore, statistically insignificant. In conclusion, it could not be ascertained whether a higher dose of CsA delays gastric emptying or whether patients with delayed emptying require higher doses of CsA. However, it is believed that determining the GET after transplantation helps in the adjustment of immunosuppressant doses.; Indications:Kidney graft rejection prophylaxis in 16 patients who underwent kidney transplantation.Patients:16 renal allograft recipients (9 men, 7 women) with a mean age of 23.18 ± 5.7 years, age range 12 to 31 and sex-matched healthy controls were enrolled in the study. All transplant recipients were taking prednisolone, Neoral, and azathioprine (n=13)/mycophenolate mofetil (n=3).TypeofStudy:The objective of this controlled clinical study was to determine the relationship between Sandimmun Neoral blood levels and gastric emptying time (GET) for semi-solid materials in stable renal transplant patient.DosageDuration:4.1 ± 1.1 mg/kg daily (range: 2 to 6 mg/kg daily) orally at 9:00 hours and 21:00 hours, always after meal. Duration 31,6 +/- 16,9 months (range 7-58 months).Results:The mean C0 concentration was 171.8 ± 56 ng/mL. The mean serum creatinine level in the recipients was 1.32 ± 0.28 mg/dL and their mean semi-solid GET (t /2) was significantly longer than that in the controls (89.1 ± 26.4 minutes versus 55 ± 15 minutes, respectively; P < .01). An analysis revealed that 12 (75%) of the 16 renal transplant recipients displayed delayed and 4 (25%) had normal semi-solid GET (t 1/2). The emptying time did not significantly correlate with the serum creatinine level, the time after transplantation, or the Sandimmun level. There was only a weak positive, but statistically insignificant, correlation between the daily Neoral dose and the GET (t1/2) (r = .33, P = .2).AdverseEffects:No adverse events were mentioned.AuthorsConclusions:In conclusion, among stable renal transplant recipients, the gastric emptying of solids was significantly slower among patients on cyclosporin A compared with healthy controls. It is believed that determining the GET after transplantation is important with respect to adjusting the doses of immunosuppressants for optimal bioavailability and therapeutic effect. Furthermore, reaching the same therapeutic effect with smaller doses of cyclosporin A reduces the cost of this expensive drug. If the immunosuppressive protocol for patients with gastroparesis contains a calcineurin inhibitor, cyclosporin A may be switched to FK-506 or coadministered with another drug that displays potent stimulatory effects on stomach and duodenal motility, such as erythromycin, other macrolides, or metoclopramide to achieve a good bioavaibility. Finally, the coadministration of these drugs may increase the bioavailabity of cyclosporin A by affecting cyclosporin A elimination by the liver P450 system.FreeText:Concomitant medications were prednisolone, azathioprine (or mycophenolate mofetil). Blood samples were obtained from each transplant recipient before the measurement of GET after an overnight fast. Neoral blood level (C0) and creatinine levels were measured by a radioimmunometric assay and by an autoanalyzer, respectively. The gastric emptying study was performed in the morning after an overnight fast. Subjects consumed a meal consisting of two scrambled eggs made from egg substitute on two pieces of bread with butter and 150 mL of water. To radiolabel the meal, 400 mcCi of 99mTc-labeled sulphur colloid was mixed into the liquid egg substitute. The labeled mixture was then scrambled in a nonstick frying pan with a portion of butter. Each meal contained 420 calories. Anterior images of the gastric region were taken within 1 minute after completion of the meal. Dynamic images were acquired at one frame per min for the next 15 minutes, and then every 15 minutes thereafter until more than half of the meal had emptied from the stomach. Images were obtained 140 kev 99mTc peak with a 20% window on a gamma camera. For each image, the gastric region was drawn manually using a computer joystick. Time-activity curves were generated from the gastric region of interest to determine the half-time ( t 1/2) for gastric emptying. If 50% of the meal had not been emptied from the stomach after 120 minutes, the acquisition was continued until 50% of the meal had emptied.