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Zidovudine (AZT), the only currently approved drug for treatment of human immunodeficiency virus (HIV) in AIDS, is known to be metabolized by mammalian systems to a variety of metabolites including 3'-azido-3'-deoxy-5'-O-glucuronide (GAZT). Interferons (IFNs) are known to alter the microsomal enzyme system responsible for the metabolism of some compounds. The aim of the present study was to investigate the effect of combination therapy of recombinant (r) IFN-beta and AZT on the rates of metabolism of AZT in AIDS patients. AZT was given orally (200 mg every 4 h) for 8 weeks prior to initiation of rIFN-beta therapy (45 X 10(6) U/day, s.c.). Serum samples from 8 patients were obtained prior to and at days 3 and 15 following initiation of rIFN-beta therapy. Serum was analyzed by high-performance liquid chromatography (HPLC) for both AZT and GAZT. The serum data were analyzed by a computer-assisted pharmacokinetics program that calculates rates of AZT metabolism. The half life for AZT was increased approximately two-fold by day 15. The rate of metabolism of AZT was diminished from 1.43 h-1 prior to IFN-beta therapy, to 0.4 h-1 and 0.05 h-1 at days 3 and 15, respectively. The volume of distribution of AZT was 2 l/kg at day 0 and increased to 3.2 and 3.5 l/kg on days 3 and 15, respectively. In conclusion, the results indicate that rIFN-beta inhibits the rate of AZT metabolism in AIDS patients.

Patent ductus arteriosus (PDA) in premature infants is a current challenge to pediatricians. Pharmacological closure of PDA with indomethacin, a prostaglandin synthetase inhibitor is an effective drug therapy, along with usual medical treatment. Administration of indomethacin may decrease mortality and morbidity (e.g. bronchopulmonary dysplasia) among very small premature infants (< 1,000 g). Co-administration of furosemide with indomethacin may lessen the transient renal side effects of indomethacin. The therapeutic efficacy of indomethacin in closure of PDA depends largely on understanding and manipulation of the pharmacokinetic characteristics of the drug in preterm infants. Maintaining a therapeutic level of the drug in plasma is essential to achieve an optimal therapeutic response. Compared to surgical ligation, indomethacin is a noninvasive, less expensive and safer therapy for ductus closure.

Summary: A rapid and sensitive high perfbrmance liquid Chromatographie method was developed for Separation and quantitation of acetaminophen, salicylic acid and salieyluric acid in human plasma and urine. The method involved ethyl acetate extraction of the three drugs from plasma or urine followed by evaporation of the organic solvent phase and dissolution of the residue in 100 methanol. A 20 aliquot was analysed on a reversed phase column using an isocratic System of 60 ml/l acetonitrile in 4 mmol/1 phosphate buffer, pH 5.7 äs a mobile phase and a variable wave length UV detector se\ at 237 nm. The procedure was used to determine the amounts of the three compounds in plasma and urine of two healthy volunteers who ingested 650 mg of aspfrin® followed one hour later by 650 mg of acetaminophen.