Excretion of cyclosporine and its metabolites in human bile.

Quantitative and qualitative studies of cyclosporine and its metabolites were performed on human bile from liver transplant and liver disease patients. The concentration of CsA in bile is higher in patients with normal liver function than in those with poor liver function but in neither case could account for more than 2% of an absorbed dose of CsA. Although concentrations of CsA plus metabolites in bile measured by RIA were 18 to 36 times higher than HPLC concentrations, they accounted for less than 50% of an absorbed CsA dose.

Cyclosporine trough concentration monitoring in liver transplant patients.

Trough blood or plasma concentration measurements of CsA must be carefully interpreted in OLT patients in relation to hepatic function, sample timing, assay specificity, and concurrent drug therapy. The RIA:HPLC ratio of blood or plasma measurements will vary with the patient's liver function, the time of blood sampling in reference to the time of drug administration, the absolute CsA concentration, and concurrent use of drugs that may alter the metabolism of CsA. The RIA assay should be used in conjunction with HPLC for trough blood or plasma measurement during the first postoperative weeks, during periods of changing hepatic function, and during changing drug regimens.

Cyclosporine pharmacokinetic profiles in liver, heart, and kidney transplant patients as determined by high-performance liquid chromatography.

Cs pharmacokinetic profiles using HPLC have aided in predicting necessary dosage alterations for specific groups of transplant patients. Additional information has been gained by HPLC profiles in nontransplant subjects who are healthy or have a stable disease state. The clinician now knows that liver disease not only impairs Cs elimination but may also have a pronounced effect upon drug absorption.

Leaching of diethylhexyl phthalate from polyvinyl chloride bags into intravenous cyclosporine solution.

The release of diethylhexyl phthalate (DEHP) from flexible polyvinyl chloride containers into intravenous cyclosporine solutions was studied. Intravenous cyclosporine solution or solutions containing the vehicle Cremophor EL and alcohol in dextrose were prepared in an all-glass system and stored in polyvinyl chloride (PVC) bags. Four samples were obtained at different time intervals, and DEHP content was analyzed by gas chromatography.

Cyclosporine absorption following orthotopic liver transplantation.

Blood concentrations of cyclosporine were determined in adult and pediatric patients following orthotopic liver transplantation to quantitate cyclosporine blood clearance and oral absorption. Seventeen bioavailability studies were performed following transplantation surgery in nine children and seven adults. The intravenous cyclosporine study was performed following an average dose of 2.

Cyclosporine monitoring.

Cyclosporine is an important immunosuppressive agent in organ and bone marrow transplantation. The pharmacokinetics of cyclosporine are quite complex and are complicated by the availability of two assay systems that yield differing results. This article summarizes the views from two major solid organ transplant centers and one bone marrow transplant center on important cyclosporine monitoring questions.

Sensitive high-performance liquid chromatographic analysis of plasma vitamin E and vitamin A using amperometric and ultraviolet detection.

A highly sensitive high-performance liquid chromatographic assay using amperometric detection has been developed for measuring alpha-tocopherol in plasma. Other minor components of vitamin E (beta-, gamma- and delta-tocopherols) can also be detected by this method. All-trans-retinol is simultaneously monitored by UV detection at 313 nm.

Effect of bile on cyclosporine absorption in dogs.

Oral absorption of cyclosporine was studied in dogs with and without bile diversion. Blood and bile cyclosporine concentrations were determined by a high pressure liquid chromatographic method. The absorption of cyclosporine was significantly impaired (p less than 0.

Cyclosporine concentration determinations for monitoring and pharmacokinetic studies.

The availability of the immunosuppressant cyclosporin has led to significant improvements in the recent success of clinical organ transplantation. Problems associated with cyclosporine therapy include serious adverse reactions, such as nephrotoxicity, wide variability in the drug's pharmacokinetics, and several complex drug interactions. Monitoring of drug concentrations is accepted as a part of the routine care of patients receiving cyclosporine.

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.

Stability and availability of cyclosporine stored in plastic syringes.

The stability and availability of cyclosporine from the oral dosage form when stored in plastic syringes were examined. Solutions of cyclosporine were stored in plastic syringes for 28 days at 25 degrees C. Half of the solutions remained in room light, and samples were obtained at 3, 6, and 12 hours and 1, 2, 3, 4, 5, 6, 7, 14, 21, and 28 days.

Clinical pharmacokinetics of cyclosporin.

Cyclosporin (cyclosporin A) is a unique immunosuppressant used to prevent the rejection of transplanted organs and to treat diseases of autoimmune origin. Therapeutic drug monitoring of cyclosporin is essential for several reasons: wide variability in cyclosporin pharmacokinetics has been observed after the oral or intravenous administration of the drug. The variability in the kinetics of cyclosporin is related to a patient's disease state, the type of organ transplant, the age of the patient and therapy with other drugs that interact with cyclosporin; maintaining a blood concentration of cyclosporin required to prevent rejection of the transplanted organ; minimising drug toxicity by maintaining trough concentrations below that which toxicity is most likely to occur; and monitoring for compliance since patient non-compliance with drug regimens is a significant reason for graft loss after 60 days.

Stability and availability of cyclosporine in 5% dextrose injection or 0.9% sodium chloride injection.

The stability of cyclosporine in commonly used i.v. solutions and the percentage of the drug delivered via polyvinyl chloride administration tubing were studied.

Quinidine dosage in children using population estimates.

A total of 36 plasma quinidine concentrations from nine hospitalized pediatric patients with cardiac arrhythmias were examined retrospectively to determine factors significantly affecting quinidine dosing. Each plasma quinidine concentration was obtained after at least 24 h of inpatient therapy. Doses of quinidine base varied from 7.

Cyclosporine kinetics in renal transplantation.

The pharmacokinetics of cyclosporine were evaluated in 41 recipients of a cadaveric renal transplant. Cyclosporine was taken by mouth (mean dose 14 mg/kg) on one study day and was intravenously infused over 2 hours (mean dose 4.7 mg/kg) on the next study day.

The effect of food on cyclosporine absorption.

The effect of food on the absorption of cyclosporine was evaluated in 18 recipients of cadaveric renal transplants. Cyclosporine was administered orally with a standard hospital breakfast on one study day and without breakfast on the alternate study day. The oral absorption rate as measured by the observed time to peak concentration was not significantly altered by food.

Anaphylactoid reactions associated with parenteral cyclosporine use: possible role of Cremophor EL.

Acute anaphylactoid reactions occurred immediately after initiation of intravenous infusions of cyclosporine in three patients post-organ transplantation. Shortness of breath, flushing, tachypnea, chest pain, pruritus, or urticaria were noted; rapid recovery followed cessation of drug infusion. Subsequently, oral cyclosporine has been used in each patient without recurrence of the observed reaction.