Therapeutic drug monitoring renal failure

Myre SA, McCann J, First MR, Cluxton RJ, Jr. Effect oftrimethoprim on serum creatinine in healthy and chronic renal failure volunteers. Therapeutic drug monitoring. 1987 Jun 9(2) 161-5. 

After transplantation, immunosuppression must be used to prevent host rejection of the graft liver, usually with prednisone and tacrolimus or cyclosporine. Tacrolimus and cyclosporine are calcineurin inhibitors and require drug level monitoring because of a narrow therapeutic range and significant toxicity, including renal failure and neurotoxicity. 

Because fluoroquinolones have a wide therapeutic index and dose-dependent toxicity, routine drug monitoring is not indicated. Monitoring fluoroquinolone concentration is indicated in renal failure, which wfll cause fluoroquinolones to accumulate. Optimal response occurs when serum concentration exceeds 1.5 Llg/mL. Activity is maintained as long as the trough concentration is >0.2flg/mL. Coadministration with antacids, ferrous sulfate, food, or sucralfate reduces absorption by 30% to 60%. Co-administration with morphine reduces absorption by >50%. 

In addition to characterization of disease states, NMR-based metabonomic analysis offers an efficient means to monitor the response of patients to drug therapy or other therapeutic interventions. For example, in a study of patients with end-stage renal failure, the response of patients to hemodialysis was monitored. Plasma samples were obtained from healthy subjects and from patients with renal failure immediately preceding and following hemodialysis. Samples were analyzed by NMR spectroscopy and mapped with pattern-recognition methods. Samples obtained from the majority of patients following hemodialysis were observed to map more closely to the cluster of samples obtained from healthy subjects than those samples obtained prior to dialysis therapy, with the exception of one patient who responded badly to the therapy and mapped separately to all other samples [13]. Thus, this methodology can be used to select appropriate therapies for patients. 

Serum drug concentrations should be monitored for drugs with narrow therapeutic indices and ehminated largely by the kidney (e.g., aminoglycosides and vancomycin) to optimize therapy in pediatric patients with renal dysfunction. For drugs with wide therapeutic ranges (e.g., penicillins and cephalosporins), dosage adjustment may be necessary only in moderate to severe renal failure. 

Hydroxychloroquine lacks the myelosuppressive, hepatic, and renal tox-icities seen with some other DMARDs, which simplifies monitoring. Its onset may be delayed for up to 6 weeks, but the drug should not be considered a therapeutic failure until after 6 months of therapy with no... 

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