UNLABELLED: A double-blind, randomized, placebo-controlled study assessed the effects of sertraline on the pharmacokinetics and pharmacodynamics of phenytoin in 30 healthy male volunteers. METHOD: All subjects received phenytoin throughout the study. The dose of phenytoin was 100 mg three times daily; steady-state trough plasma phenytoin concentrations were determined on Day 6. Concurrent treatment with sertraline (16 subjects) or placebo (13 subjects) was initiated on Day 8 and continued throughout the study in those subjects whose trough plasma phenytoin concentrations were between 5 and 20 micrograms/mL. The dose of sertraline was increased from 50 to 200 mg/day over 7 days; the 200-mg dose was then administered for 10 days. The plasma phenytoin concentration-time profile was determined on Day 7 before the start of sertraline or placebo dosing and at the end of dosing on Day 24. Psychometric testing was done before and after dosing on Days 0, 7, and 24. RESULTS: There were no significant differences between the sertraline group and the placebo group in the pharmacokinetic parameters of phenytoin. In addition, there was no indication that administration of phenytoin alone or concomitant administration of phenytoin and sertraline impaired cognitive function. Treatment-related side effects, primarily headache and nausea, were reported in 8 of 16 sertraline subjects and in 5 of 13 placebo subjects. Two subjects in the sertraline group withdrew because of side effects (rash), and 3 subjects in the placebo group withdrew because of side effects (rash and headache). CONCLUSION: High dosages of setraline did not affect the pharmacokinetics or the pharmacodynamics of phenytoin in ths study performed in healthy volunteers.

1-Naphthylamine↗

PubMed1996

Antigenic variation in trypanosomes.

We review here antigenic variation in African trypanosomes with emphasis on genetic mechanisms and on the expression sites in which the genes for Variant Surface Glycoproteins (VSGs) are expressed. There are multiple expression sites in a trypanosome, but only one of these is active at a time. We discuss recent experiments that provide new information on expression site regulation, i.e., how inactive sites are kept inactive and how the trypanosome switches from expression of one site to expression of another one. Trypanosomes can also change the gene expressed by replacing the gene in an active expression site by another VSG gene. This replacement involves the duplicative transposition of a silent VSG gene into the expression site. We present a model for the mechanism of this transposition that incorporates new features and that explains several unusual characteristics of the transposition process. We also discuss how new knowledge of nutrient uptake, notably uptake of host transferrin by trypanosomes, might be used for vaccine development.

Animals↗

PubMed1995