Abstract
Preliminary reports suggest an interaction exists between theophylline and mexiletine. We conducted a two-way crossover study in 15 healthy male subjects to assess the magnitude of the pharmacokinetic interaction between mexiletine and theophylline. Twelve subjects completed 5 days of therapy on sustained-release theophylline 200 mg every 12 hours alone and 5 days of therapy with theophylline and mexiletine 150 mg every 8 hours. The two treatment periods were separated by a minimum of 7 days. On the morning of day 5 of each treatment period, blood samples for theophylline to be assayed by fluorescence immunoassay were collected over 24 hours. Mexiletine significantly increased the mean AUC, Cmax, t 1/2 β, and Cl of theophylline. Mexiletine did not affect tmax or Vd. Side effects occurred in 4 subjects during treatment with theophylline alone all of which were judged to be mild in intensity. During concomitant theophylline-mexiletine therapy, 10 subjects reported side effects of which 4 were judged to be severe, 1 moderate, and 5 mild. The magnitude of the increase in theophylline plasma concentrations induced by mexiletine as measured by AUC (0-24) was 58%, which is similar to other preliminary reports of this interaction. The authors conclude that the magnitude of the pharmacokinetic interaction between theophylline and mexiletine may be clinically significant in patients in light of the increased incidence of side effects in our healthy subjects. Theophylline dosage adjustments will be required in patients who receive concomitant mexiletine therapy.
| Original language | English |
|---|---|
| Pages (from-to) | 354-357 |
| Number of pages | 4 |
| Journal | Journal of Clinical Pharmacology |
| Volume | 31 |
| Issue number | 4 |
| State | Published - 1991 |
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All Science Journal Classification (ASJC) codes
- Pharmacology (medical)
- Pharmacology, Toxicology and Pharmaceutics(all)
Cite this
Influence of mexiletine on the pharmacokinetics of theophylline in healthy volunteers. / Stoysich, A. M.; Mohiuddin, Syed M.; Destache, Christopher J.; Nipper, H. C.; Hilleman, Daniel E.
In: Journal of Clinical Pharmacology, Vol. 31, No. 4, 1991, p. 354-357.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Influence of mexiletine on the pharmacokinetics of theophylline in healthy volunteers
AU - Stoysich, A. M.
AU - Mohiuddin, Syed M.
AU - Destache, Christopher J.
AU - Nipper, H. C.
AU - Hilleman, Daniel E.
PY - 1991
Y1 - 1991
N2 - Preliminary reports suggest an interaction exists between theophylline and mexiletine. We conducted a two-way crossover study in 15 healthy male subjects to assess the magnitude of the pharmacokinetic interaction between mexiletine and theophylline. Twelve subjects completed 5 days of therapy on sustained-release theophylline 200 mg every 12 hours alone and 5 days of therapy with theophylline and mexiletine 150 mg every 8 hours. The two treatment periods were separated by a minimum of 7 days. On the morning of day 5 of each treatment period, blood samples for theophylline to be assayed by fluorescence immunoassay were collected over 24 hours. Mexiletine significantly increased the mean AUC, Cmax, t 1/2 β, and Cl of theophylline. Mexiletine did not affect tmax or Vd. Side effects occurred in 4 subjects during treatment with theophylline alone all of which were judged to be mild in intensity. During concomitant theophylline-mexiletine therapy, 10 subjects reported side effects of which 4 were judged to be severe, 1 moderate, and 5 mild. The magnitude of the increase in theophylline plasma concentrations induced by mexiletine as measured by AUC (0-24) was 58%, which is similar to other preliminary reports of this interaction. The authors conclude that the magnitude of the pharmacokinetic interaction between theophylline and mexiletine may be clinically significant in patients in light of the increased incidence of side effects in our healthy subjects. Theophylline dosage adjustments will be required in patients who receive concomitant mexiletine therapy.
AB - Preliminary reports suggest an interaction exists between theophylline and mexiletine. We conducted a two-way crossover study in 15 healthy male subjects to assess the magnitude of the pharmacokinetic interaction between mexiletine and theophylline. Twelve subjects completed 5 days of therapy on sustained-release theophylline 200 mg every 12 hours alone and 5 days of therapy with theophylline and mexiletine 150 mg every 8 hours. The two treatment periods were separated by a minimum of 7 days. On the morning of day 5 of each treatment period, blood samples for theophylline to be assayed by fluorescence immunoassay were collected over 24 hours. Mexiletine significantly increased the mean AUC, Cmax, t 1/2 β, and Cl of theophylline. Mexiletine did not affect tmax or Vd. Side effects occurred in 4 subjects during treatment with theophylline alone all of which were judged to be mild in intensity. During concomitant theophylline-mexiletine therapy, 10 subjects reported side effects of which 4 were judged to be severe, 1 moderate, and 5 mild. The magnitude of the increase in theophylline plasma concentrations induced by mexiletine as measured by AUC (0-24) was 58%, which is similar to other preliminary reports of this interaction. The authors conclude that the magnitude of the pharmacokinetic interaction between theophylline and mexiletine may be clinically significant in patients in light of the increased incidence of side effects in our healthy subjects. Theophylline dosage adjustments will be required in patients who receive concomitant mexiletine therapy.
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UR - http://www.scopus.com/inward/citedby.url?scp=0025843510&partnerID=8YFLogxK
M3 - Article
C2 - 2037708
AN - SCOPUS:0025843510
VL - 31
SP - 354
EP - 357
JO - Journal of Clinical Pharmacology
JF - Journal of Clinical Pharmacology
SN - 0091-2700
IS - 4
ER -