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Biomedical subjects

J Knepil

Publications and source records attributed to J Knepil.

At least 19 recordsLinked to original sources

Methotrexate removal during haemodialysis in a patient with advanced laryngeal carcinoma.

A 62-year-old patient on long-term haemodialysis who developed an inoperable T2N3Mo squamous-cell carcinoma of the larynx was treated with weekly low-dose methotrexate (MTX) after failing to respond to radiotherapy. The patient was initially given one dose of 10 mg MTX (6 mg/m2) as a 1-h infusion, then he received three further i.v. doses of 20 mg (12 mg/m2). Haemodialysis was performed 15-18 h after each dose and the patient received folinic acid (30 mg i.v.q 6 h) until the MTX concentration was < 0.1 mumol/l. The MTX concentration was measured regularly until it reached < 0.1 mumol/l, and additional samples were withdrawn pre- and post-dialysis. The MTX elimination rate constant and half-life were estimated with the patient on and off dialysis. The patient failed to respond to treatment but did not experience MTX-related toxicity. The elimination half-life ranged from 22 to 42 h when he was off dialysis but fell to a median of 5.5 h during dialysis. Low-dose MTX was given to a patient on regular haemodialysis without evidence of toxicity. The rate of MTX elimination was increased during haemodialysis, although high MTX concentrations persisted for several days and prolonged rescue with folinic acid was required.

Antimetabolites, Antineoplastic↗

Evaluation of a Bayesian approach to the pharmacokinetic interpretation of cyclosporin concentrations in renal allograft recipients.

The utility of a Bayesian parameter estimation program in the interpretation of cyclosporin concentrations was investigated in a group of 32 patients following renal transplantation. The program was evaluated by comparing concentrations predicted from individual estimates of pharmacokinetic parameters with measured concentrations. A one-compartment model incorporating an exponential, time-related change in clearance was used for data collected in the first 4 weeks after transplantation, and predictions of concentrations measured during weeks 5-14 were made using three schemes: a changing clearance model using all data from week 1 onward; a changing clearance model using data from week 4 onward; and a nonchanging clearance model using data from week 4 onward. Results demonstrated that predictions made by the Bayesian program were unreliable during the first 4 weeks of therapy, but that there was a progressive improvement as time after transplantation increased. The changing clearance model was superior to the constant clearance model and its performance was not compromised by including data from the first 4 weeks of therapy. Although the Bayesian approach may help with the interpretation of blood cyclosporin concentrations during maintenance therapy, the large variability in the pharmacokinetics of orally administered cyclosporin limits the usefulness of the approach in the early weeks following transplantation.

Adult↗

Water balance.

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Body Water↗