Effect of over-the-counter cimetidine on phenytoin concentrations in patients with seizures.
OBJECTIVE
To determine the effects of the maximum recommended over-the-counter (OTC) cimetidine dosage on phenytoin concentrations in ambulatory seizure patients on long-term phenytoin therapy.


METHODS
Adults with seizure disorders requiring phenytoin therapy were recruited. Trough total phenytoin concentrations were measured initially and once weekly for six weeks. All assays were performed using Biotrack patient-side cartridges. After a two-week baseline period, patients took cimetidine 200 mg twice daily for two weeks. Toxicity was monitored via weekly neurologic examinations and midweek telephone surveys. Patients were asked to return to clinic weekly during a two-week cimetidine washout period.


RESULTS
Nine patients entered and completed the study. All but two patients took other anticonvulsants known to interact with phenytoin (carbamazepine, n = 5; phenobarbital, n = 2). No adverse effects or changes in seizure frequency were reported. Paired Student's t-tests revealed no significant difference between serum phenytoin concentrations before (12.3+/-3.2 mg/L [mean +/- SD]) and after (12.8+/-4.0 mg/L) two weeks on the OTC cimetidine regimen. No differences were noted in estimated pharmacokinetic parameters (maximum metabolic rate, Michaelis-Menten constant) for the same time periods (paired Student's t-test, p > 0.05). The Biotrack assay had an r2 = 0.7311 (p < 0.001, two-sided) when compared with TDx.


CONCLUSIONS
It is possible that the lack of change in phenytoin concentrations was a result of the low daily dosage of cimetidine used or other factors related to the "real world" setting of the study. However, the potential for a serious drug interaction occurring in patients taking long-term oral phenytoin and OTC cimetidine appears to be small.
Rafi
J A
JA
School of Pharmacy, Virginia Commonwealth University, Richmond 23298, USA.
Frazier
L M
LM
Driscoll-Bannister
S M
SM
O'Hara
K A
KA
Garnett
W R
WR
Pugh
C B
CB
D000328:Adult; D000897:Anti-Ulcer Agents / Q000009:adverse effects*; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002927:Cimetidine / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010672:Phenytoin / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011237:Predictive Value of Tests; D012640:Seizures / Q000188:drug therapy / Q000378:metabolism*
D000897:Anti-Ulcer Agents; D000927:Anticonvulsants; D010672:Phenytoin; D002927:Cimetidine