Biomedical subjects

R J Ptachcinski

Publications and source records attributed to R J Ptachcinski.

41 records · Page 3Linked to original sources

PubMed1985

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. The presence of Cremophor EL as an emulsifying agent in the parenteral dosage formulation of cyclosporine is a likely etiology for this acute adverse reaction. Slowed rates of drug infusion and antihistamine premedication may permit continued intravenous cyclosporine use in affected patients.

Adult↗

PubMedDate not supplied

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.

Adult↗

PubMedDate not supplied

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 2.1 mg/kg. The patients were again studied when they received the same intravenous dose plus an oral dose of cyclosporine of 8.6 mg/kg or an oral dose alone. Blood samples were collected and analyzed for cyclosporine using high-performance liquid chromatography. Cyclosporine blood clearance ranged from 29 to 203 mL/min (1.9-21.5 mL/min/kg) in children and from 253 to 680 mL/min (3.2-7.6 mL/min/kg) in adults. The mean cyclosporine clearance value was 9.3 mL/min/kg in the pediatric patients and 5.5 mL/min/kg in the adults. Cyclosporine bioavailability was less than 5% in six studies on five pediatric patients in the immediate postoperative period. The bioavailability varied from 8% to 60% in adult liver transplant patients (mean, 27%). We conclude that: cyclosporine clearance is highly variable between patients, pediatric patients clear the drug more rapidly than adults and therefore need a higher cyclosporine dose on a body weight basis, cyclosporine is poorly and variably absorbed in liver transplant patients, and cyclosporine blood concentration monitoring is essential following orthotopic liver transplantation.

Adult↗

PubMedDate not supplied

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. However, cyclosporine concentrations can be determined in different biologic fluids by either radioimmunoassay or high-performance liquid chromatographic techniques. Controversy exists regarding the optimal analytic technique to be used for cyclosporine monitoring and pharmacokinetic studies. This commentary addresses factors including: why the monitoring of cyclosporine concentrations is important, the differences between the biologic fluids and analytic techniques, when monitoring and special pharmacokinetic studies are indicated, what some major transplant centers have established as a "therapeutic range" for cyclosporine concentrations, and provides guidelines for the optimal clinical monitoring of cyclosporine concentrations.

Adult↗

PubMedDate not supplied

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. Clinical monitoring and pharmacokinetic studies of cyclosporin can be performed using different biological fluids (plasma, serum or whole blood) and different analytical techniques (radioimmunoassay or high pressure liquid chromatography). The available analytical methods provide different results when using blood, plasma, or serum. Comparison of therapeutic ranges and pharmacokinetic parameters should be made with careful attention given to the method of cyclosporin analysis. Following oral administration, the absorption of cyclosporin is slow and incomplete. Peak concentrations in blood or plasma are reached in 1 to 8 hours after dosing. The bioavailability of cyclosporin ranges from less than 5% to 89% in transplant patients; poor absorption has frequently been observed in liver and kidney transplant patients and in bone marrow recipients. Factors that affect the oral absorption of cyclosporin include the elapsed time after surgery, the dose administered, gastrointestinal dysfunction, external bile drainage, liver disease, and food. Cyclosporin is widely distributed throughout the body. Following intravenous administration, the drug exhibits multicompartmental behaviour. The volume of distribution (whole blood; HPLC) ranges from 0.9 to 4.8 L/kg. Cyclosporin is highly bound to erythrocytes and plasma proteins and has a blood to plasma ratio of approximately 2. In plasma, approximately 80% of the drug is bound to lipoproteins. The distribution of cyclosporin in blood can be affected by a patient's haematocrit and lipoprotein profile. Cyclosporin is extensively metabolised, primarily by mono- and dihydroxylation as well as N-demethylation, and is considered a low-to-intermediate clearance drug.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗