Differential Reinforcement of Low Rate Performance, Pharmacokinetics and Pharmacokinetic-Pharmacodynamic Modeling: Independent Interaction of Alprazolam and Caffeine
To investigate the interaction between alprazolam and caffeine, performance on a differential reinforcement of low-rate behavior schedule and the respective pharmacokinetics (PK) were explored in concurrent studies. Alprazolam PK was not altered by caffeine, but alprazolam retarded caffeine absorpti...
Saved in:
Published in | The Journal of pharmacology and experimental therapeutics Vol. 281; no. 3; p. 1013 |
---|---|
Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Pharmacology and Experimental Therapeutics
01.06.1997
|
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | To investigate the interaction between alprazolam and caffeine, performance on a differential reinforcement of low-rate behavior
schedule and the respective pharmacokinetics (PK) were explored in concurrent studies. Alprazolam PK was not altered by caffeine,
but alprazolam retarded caffeine absorption indirectly, as inferred by the lack of i.v. drug administration PK interaction,
thereby decreasing serum methylxanthine concentrations. Inasmuch as alprazolam was more potent and short-lived than caffeine
in decreasing the reinforcement rate (consonant with their respective t 1/2 values, 0.44 and 3.1 hr), the alprazolam/caffeine potency ratio decreased across the session time, which determined the expression
of the combined effects. Thus, the decreased methylxanthine level yielded slightly less disruption in performance for the
observed combined effect, compared to the expected calculated effect, only near the end of a session. The interaction was
PK linked and mainly not distinguishable from independence as indicated by the Pöch dose-response curve method and the integration
of PK and pharmacodynamics. The sigmoid maximal effect-link pharmacodynamic model indicated that caffeine did not alter the
concentration at half of the maximal effect value of alprazolam and suggested that the interaction is not competitive, but
independent. Although the nature of the benzodiazepine-methylxanthine interaction has been controversial in other behavioral
studies, as is the role of PK in determining behavior, this and our previous study make it evident that the interaction is
independent not only across doses and routes of administration, but also with respect to two indices of differential reinforcement
of low rate performance. |
---|---|
ISSN: | 0022-3565 1521-0103 |