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Biomedical subjects

S S Murthy

Publications and source records attributed to S S Murthy.

23 records · Page 2Linked to original sources
PubMed1970

Feasibility of a chemoprophylaxis trial in India against tuberculosis. A pilot study.

A pilot study in Bangalore to investigate the feasibility of a chemoprophylaxis trial with isoniazid is described.For a chemoprophylaxis trial, 2 basic requirements are that a large number of participants must take the drug and that reliable estimates of the amount of drug consumed should be available. Distribution of weekly supplies of pills for self-medication was tried and actual consumption was checked by urine examination using the Belles-Littleman filter-paper spot test. Except during the first month, the proportion of positive urine samples was very small.Estimating drug consumption by "pill counting" or by means of house-to-house interview was not reliable. These methods are not recommended for a chemoprophylaxis trial in India.Direct administration of pills to each participant every day for 6 months by a locally employed person resulted in a much higher consumption of pills. In spite of some deliberate false recording and some genuine recording errors, the results are considered encouraging enough to warrant further trials. Procedures are simpler and records of consumption for each individual are available. The method also provides the opportunity to use the individual, and not the family, as the unit for randomization between treatments.The proportion of positive urine samples provides an objective means of assessing the reliability of estimates of drug intake by other methods but large numbers of urine samples would be required if this method were to be used independently for estimating individual pill consumption.

Adolescent↗
PubMedDate not supplied

Pharmacokinetic interaction between verapamil and metoprolol in the dog. Stereochemical aspects.

The effect of verapamil co-administration on the hepatic first-pass clearance of metoprolol was investigated in dogs. Plasma concentration-time course of metoprolol enantiomers and urinary recovery of oxidative metabolites were determined after a single iv (0.51 mg/kg) and an oral (1.37 mg/kg) dose of deuterium-labeled pseudoracemic metoprolol, with or without concomitant administration of racemic verapamil (3 mg/kg). Verapamil inhibited both the systemic and oral clearance of metoprolol by about 50-70%. The first-pass effect of metoprolol was completely abolished after co-administration of verapamil, reflecting a marked alteration in the degree of hepatic extraction of metoprolol from intermediate to low. The hepatic clearance of metoprolol was slightly (S)-enantioselective (R/S ratio = 0.89 +/- 0.04) in control dogs. Inhibition of hepatic clearance of metoprolol by verapamil was selective towards (S)-metoprolol, such that the enantioselectivity in hepatic clearance toward (S)-metoprolol disappeared following verapamil co-administration (R/S ratio = 1.01 +/- 0.05). Urinary metabolite profiles indicated that O-demethylation and N-dealkylation were the major pathways of oxidative metabolism in the dog. alpha-Hydroxymetoprolol was a minor metabolite in urine. N-Dealkylation showed a strong preference for (S)-metoprolol, whereas O-demethylation and alpha-hydroxylation exhibited a modest selectivity toward (R)-metoprolol; hence, the slight (S)-enantioselectivity in the overall hepatic clearance. Comparison of metoprolol metabolite formation clearances in the absence or presence of verapamil co-administration showed that all three oxidative pathways were inhibited by 60-80%. The greater inhibition of hepatic clearance observed with (S)-metoprolol as compared to (R)-metoprolol was attributed to a significant (S)-enantioselective inhibition in the O-demethylation of metoprolol by verapamil.

Administration, Oral↗