The Clearance of Cyclosporine by Hemodialysis

The pharmacokinetics of cyclosporine were studied in five liver transplant patients when they were on and off hemodialysis. There was no significant difference in the blood clearance of cyclosporine between these two periods. Less than 1 per cent of the dose of cyclosporine was recovered in the dialysate. The mean dialysis clearance was less than 1 ml/min. This represents less than 1 per cent of the total blood clearance of cyclosporine. Dosage alterations of cyclosporine during or after hemodialysis do not appear to be necessary

A prospective randomized trial comparing sequential ganciclovir-high dose acyclovir to high dose acyclovir for prevention of cytomegalovirus disease in adult liver transplant recipients

Cytomegalovirus disease is an important cause of morbidity following liver transplantation. To date there has not been an effective prophylaxis for CMV disease after liver transplantation. One hundred forty-three patients were randomized to receive either high dose oral acyclovir (800 mg 4 times a day) alone for 3 months after transplantation (acyclovir group) or intravenous ganciclovir (5 mg/kg twice a day) for 14 days followed by high dose oral acyclovir to complete a 3-month regimen (ganciclovir group). Of 139 patients available for evaluation, 43 of 71 (61%) patients from the acyclovir group developed CMV infection compared with 16 of 68 (24%) from the ganciclovir group (relative risk, 3.69; 95% confidence interval, 2.07-6.56; PcO.OOOOl). Of those randomized, CMV disease was seen in 20 (28%) of the acyclovir group compared with 6 (9%) of the ganciclovir group (relative risk, 5.11; 95% confidence interval, 2.05-12.75; P=0.0001). The median time to onset of CMV infection was 45 days in the acyclovir group compared with 78 days in the ganciclovir group (P=0.004). The median time to onset of CMV disease was 40 days in the acyclovir group compared with 78 days in the ganciclovir patients (P=0.02). With respect to primary CMV infection, there was no difference in the rates in the 2 groups, but tissue invasive disease and recurrent CMV disease were less frequent in the ganciclovir group. It is concluded that a course of 2 weeks of ganciclovir immediately after transplantation followed by high dose oral acyclovir for 10 weeks is superior to a 12-week course of high dose oral acyclovir alone for prevention of both CMV infection and CMV disease after liver transplantation. However, the lack of significant effect in seronegative recipients who received grafts from seropositive donors suggests that other strategies are needed to prevent CMV infection in this high risk population. © 1994 by Williams & Wilkins

Antipyrine kinetics in liver disease and liver transplantation

Antipyrine kinetics were studied in seven normal subjects, 10 patients with liver disease, and 13 clinically stable patients who received a liver transplant. Five patients were studied both before and after liver transplantation. Antipyrine concentrations in saliva after oral dosing were measured by HPLC. The antipyrine t(1/2) was significantly longer (P < 0.05) in patients with liver disease than in patients undergoing liver transplantation and normal subjects. Antipyrine clearance was not significantly different between patients undergoing liver transplantation and normal subjects, but it was significantly reduced (P < 0.05) in patients with liver disease. In five patients who were studied before and after liver transplantation, there was a significant (P < 0.05) increase in the antipyrine clearance and a marked reduction in its t(1/2) after liver transplantation. These results indicate that liver transplantation improves the drug metabolizing ability of patients with liver disease and that the oxidative metabolizing capacity of the liver in clinically stable patients after liver transplantation is similar to that of normal subjects

In-vitro Interaction of a Novel Immunosuppressant, FK 506, and Antacids

Abstract-The effect of selected antacids on the amount ofFK 506 in solution in simulated gastric juice has been studied. FK 506 (2·5 mg) was incubated in 100 mL simulated gastric fluid (SGF) with the equivalent of 500 mg of various antacids. The addition of Mylanta and Turns resulted in 14 and 30&apos;1., loss of FK 506, respectively, in 24 h; 98% loss was observed in 12 h in the presence of Mag-Ox; 100&apos;Yo loss was observed in the presence of magnesium oxide powderin 2 h. The loss ofFK 506 from these solutions appears to be due to a pH mediated degradation of FK 506. The addition of aluminium hydroxide gel USP (Roxane) to the FK 506 solution resulted in a 35°;;, loss within 2 min but no further loss was noted for 24 h. indicative of adsorption ofFK 506. These results suggest that until additional in-vivo studies are carried out. it is prudent not to dose FK 506 and antacids at the same time to avoid potential interactions

Utility of Urine Cultures During Febrile Neutropenia Workup in Hematopoietic Stem Cell Transplantation Recipients Without Urinary Symptoms

The utility of obtaining screening urine cultures for febrile neutropenia (FN) during hematopoietic stem cell transplant (HCT) is unknown. In 667 adult HCT patients with FN, only 40 (6%) were found with bacteriuria. Antibiotics were modified in 3 patients (0.4%) based on urine cultures and none developed urinary-associated infectious complications