STABILITY OF DRUG ADDITIVES TO PERITONEAL DIALYSATE

Objective: The primary literature was reviewed to determine the stabil ity of drug additives in peritoneal dialysis solutions. Data Sources: A MEDLINE search and retrieval, covering the period 1981 to 1994, was undertaken to identify relevant original literature. Additional refere nces were identified from citations within the original literature. No n-English literature was excluded unless an English abstract was provi ded. Study Selection: Forty-nine studies were identified. Of these, 24 were directly related to drug stability, 13 were related to the clini cal use of the drug additives but included no stability data, and 12 e xamined other, nonstability aspects of in vitro activity of antibiotic s, additives, or drug adsorption in peritoneal dialysis bags and tubin g. Data Extraction: Data included concentrations of drug additives and dialysate solutions, duration and temperatures of storage conditions, types of assay, and whether they were stability-indicating. Results: Stability was defined as the duration of time that the drug concentrat ion remained at 90% or more of the original concentration. Stability w as examined under a large variety of conditions. Thirty-one drugs were identified from 20 manuscripts as single-drug additives. Most beta-la ctams were stable for 1 - 2 weeks in a refrigerator and for several da ys at room temperature. Aminoglycosides were stable for 1 - 2 days at room temperature. Glycopeptides were stable for several weeks refriger ated or at room temperature. Prolonged storage at room temperature res ulted in instability of cefotaxime, ceftazidime, ceftriaxone, and mico nazole. Eleven drugs were identified from seven manuscripts as drug co mbination studies and showed similar stability as single agents. Dialy sate concentration appeared to have minimal effect on stability. Concl usions: Drug additives in peritoneal dialysate, singly or combined, sh ould be avoided unless data are available to support their stability. Additives should be made as close as possible to the time of the excha nge. Alternatively, additives should be stored refrigerated, then warm ed prior to use. The practice of preparing numerous bags at one time s hould be avoided. Finally, stability data do not indicate sterile inte grity of the dialysate.