The individual enantiomers of cimetidine sulfoxide were resolved by preparative chromatography using a Chiralcel OC stationary phase and were characterized by the determination of optical rotation and circular dichroism spectra. Cimetidine sulfoxide was isolated from the urine of two healthy male volunteers following oral administration of cimetidine (400 mg). Urine was collected every 2 h for 12 h postdosing, after which time HPLC analysis indicated negligible recovery of the drug as the sulfoxide. Some 7% of the dose was recovered as cimetidine sulfoxide over this period. The enantiomenc composition of cimetidine sulfoxide was determined by sequential achiral-chiral chromatography using the OC phase. Over the collection period the enantiomeric ratio was found to be constant in all samples at (+/-I of 71 * 2.5:29 2 2.5. The enantiomeric composition of cimetidine sulfoxide was also determined in rat urine (24 h) following the administration of cimetidine (30 mgkg PO) to male Wistar rats (n = 7). The enantiomeric ratio in this case was found to be (+I-) 57 2 2.3:43 k 2.3. These preliminary data indicate that sulfoxidation of cimetidine is stereoselective with respect to the (+)-enantiomer and that species variation in enantiomeric composition occurs. The metabolism and disposition of cimetidine have been investigated in standard laboratory species, i.e., rat, dog, guinea pig, and also in man."-" Following oral administration to man, cimetidine is known to be well absorbed from the gastrointestinal tract, with the majority of an oral dose (ca. 80%) being eliminated in the urine within 24 h. A further 4% appears in the feces, drug recovery being essentially quantitative within 3 days. The majority of the material recovered in human urine is as unchanged drug (ca. 50% of the dose), with the residual material being recovered as metabolic products, namely 5-hydroxymethylcimetidine, cimetidine sulfoxide (Fig. l), cimetidine guanylurea, and cimetidine-N'-glucuronide. Of these metabolites, the sulfoxide is quantitatively the most important oxidation product." Similarly, of the material eliminated in the feces, the majority is as unchanged drug (>75%), or the sulfoxide (ca. 22%)." An additional metabolite, N-desmethylcimetidine, has been identified following incubation of cimetidine with rat liver microsomal preparations. However, to date this compound has not been identified in in vivo studies.0 1994 Wilev-Liss, Inc.

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The piloting of the Fundamentals of Palliative Care program at this single site was of benefit and relevance to participants in their clinical practice. Overall, participants felt the course was useful to them and that they were able to gain valuable knowledge and skills. Several areas could be refined to optimize the learning, including: (1) knowing attendee learning potentialities and prior experiences, (2) considering a more inclusive and formal assessment process, (3) creating diverse mechanisms for disseminating knowledge and skills, and (4) improving methods of evaluation.

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