Resolution of concentration-response differences in onset of effect between subcutaneous and oral sumatriptan.
OBJECTIVE
To investigate whether the concentration-response relationships for onset of effect of oral and subcutaneous (s.c.) sumatriptan differ, and if so, then to explore whether a single model for the onset of effect can nonetheless be found for multiple dose sizes and both routes of administration.


METHODS
Active and placebo response rates and mean plasma concentrations were collected from the literature for 0 < or =t < or = 2 hours. Plasma concentration-response relationships were plotted. Logarithmic models for the onset of effect (ie, active response rates), characterized by convexity factor A and location parameter B were constructed from the same data.


RESULTS
The concentration-response relationships for s.c. and oral sumatriptan are qualitatively different. A single logarithmic model for the onset of effect provides good estimates of observed response rates during the first 2 hours post-dose for multiple dose sizes after both oral and s.c. routes of administration. The precision of this model resides in both its variables. Location parameters for this model differ for similar absolute doses by the two routes of administration. However, curve convexity (representing rate of onset of effect) is related to absolute dose (and hence plasma concentration) in the same way for sumatriptan tablets and injections.


CONCLUSIONS
No simple plasma concentration-response relationship exists that is sufficiently robust to apply to both s.c. and oral sumatriptan. There are separate pharmacokinetic-pharmacodynamic relationships for rate of onset and extent of effect. The design of exploratory clinical trials for new acute therapies for migraine may be more efficient when these factors are considered, and these factors may help to describe the gap between experimental and ordinary clinical environments.
Freidank-Mueschenborn
Edda
E
Biostatistics and Data Management, Engelhard Arzneimittel GmbH, Niederdorfen, Hessen, Germany.
Fox
Anthony W
AW
D000284:Administration, Oral; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007279:Injections, Subcutaneous; D008954:Models, Biological; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D018170:Sumatriptan / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*
D017366:Serotonin Receptor Agonists; D018170:Sumatriptan