Assessment of potential drug-drug interactions at hospital discharge.

OBJECTIVE: The evaluation of the prevalence of potential drug-drug interactions and assessment of their clinical relevance in patients' discharge medication in the medical ward of a community teaching hospital. The relevant clinical information was reported to the treating physicians. METHODS: 200 patients at discharge from a medical ward were included. Prescribed drugs were analysed for interactions using commercially available software (Pharmavista). Clinical pharmacists and a physician assessed the clinical relevance of detected interactions, eliminated those which were not considered clinically relevant and formulated recommendations for those considered clinically relevant. A written recommendation was given to the physician to provide rapid feedback before discharge. RESULTS: The median age of the 200 patients studied was 69 years. At discharge, patients took an average of 7 different drugs. 62.5% of patients had at least one potential drug-drug interaction. In total, 373 potential drug-drug interactions were identified: 223 (60%) of minor severity, 143 (38%) of moderate severity and 7 (2%) of major severity. CONCLUSIONS: A computerised drug-drug interaction program (detection) together with clinical pharmacological experience (interpretation/evaluation) can be useful for decreasing the number of potentially harmful drug combinations. This approach may lead to an improvement in the quality of prescription, reducing possible risks and thus contributing to patient safety.

Expression of rat renal sulfate transport systems in Xenopus laevis oocytes. Functional characterization and molecular identification.

Renal proximal tubular sulfate reabsorption is mediated by brush border membrane Na+/sulfate-cotransport and basolateral Na(+)-independent sulfate transport. Injection of rat kidney cortex mRNA into Xenopus laevis oocytes induced Na(+)-dependent as well as Na(+)-independent sulfate transport. The inhibition pattern of Na(+)-dependent uptake coincided with that known for the brush border membrane; the inhibition pattern of Na(+)-independent uptake suggested that this activity could be related to the basolateral cell surface. By Northern blot hybridization of size-fractionated mRNA, we provide evidence that the Na(+)-dependent uptake is induced by an mRNA species related to a recently cloned cDNA encoding rat renal cortex Na+/SO4 cotransport (NaSi-1; Markovich, D., Forgo, J., Stange, G., Biber, J., and Murer, H. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 8073-8077); the Na(+)-independent sulfate transport activity seems to be related to an mRNA species encoding a rat liver Na(+)-independent sulfate transporter (Bissig, M., Hagenbuch, B., Stieger, B., Koller, T., and Meier, P. J. (1994) J. Biol. Chem. 269, 3017-3021). Hybrid depletion experiments using antisense oligonucleotides provided further evidence for the association of the expressed transport activities to NaSi-1 and sat-1, respectively.

Functional expression cloning of the canalicular sulfate transport system of rat hepatocytes.

We have cloned a single cDNA encoding the canalicular sulfate transporter of rat liver using Xenopus laevis oocytes as a functional expression system. The cloned cDNA sulfate anion transporter-1 (sat-1) expresses saturable Na(+)-independent sulfate uptake (Km approximately 0.14 mM) that can be inhibited by 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene (DIDS, IC50 = 28 microM) and oxalate, but not by succinate or cholate. These properties are very similar to sulfate uptake expressed in oocytes injected with total rat liver mRNA and to the bicarbonate/sulfate exchange system previously characterized in canalicular rat liver plasma membrane vesicles. The cloned sat-1 cDNA has a total length of 3726 base pairs (bp) with an open reading frame encompassing 2109 bp, a 5'-untranslated region of 367 bp, and a 3'-untranslated region of 1250 bp. The coding region predicts a protein of 703 amino acids with a calculated molecular mass of 75.4 kDa. Computer-based hydrophobicity analysis suggests the presence of 12 putative transmembrane spanning domains. Furthermore, three potential glycosylation sites are detected (Asn-158, Asn-163, Asn-587). Northern blot analysis indicates that similar sulfate anion transporters are also present in the kidney, muscle, and brain of rat and in the liver of the mouse. Using antisense oligonucleotides the mRNA-species of the sat-1 analogue in rat kidney has been characterized by hybrid depletion experiments (Markovich, D., Bissig, M., Sorribas, V., Hagenbuch, B., Meier, P. J., and Murer, H. (1994) J. Biol. Chem. 269, 3022-3026).