Effect of ciprofloxacin and grapefruit juice on oral pharmacokinetics of riluzole in Wistar rats.
OBJECTIVE
The objective of this study was to explore potential drug-drug/food interactions of ciprofloxacin and grapefruit juice, known hepatic cytochrome P450 (CYP) 1A2 inhibitors, on single-dose oral pharmacokinetics of riluzole, a substrate of CYP 1A2 enzymes.


METHODS
Pharmacokinetic parameters of riluzole were determined in Wistar rats after single-dose co-administration with ciprofloxacin and grapefruit juice. In-vitro metabolic inhibition studies using rat and human liver microsomes and intestinal absorption studies of riluzole in a rat everted gut-sac model were conducted to elucidate the mechanism of interaction. A validated HPLC method was employed to quantify riluzole in the samples obtained in various studies.


RESULTS
Co-administration of ciprofloxacin with riluzole caused significant increase in systemic exposure of riluzole (area under the curve, maximum plasma concentration and mean residence time were found to increase). Co-administration of grapefruit juice with riluzole did not cause any significant difference in the pharmacokinetic parameters of riluzole. In-vitro metabolism studies demonstrated significant inhibition of riluzole metabolism when it was co-incubated with ciprofloxacin or grapefruit juice. No significant change was observed in apparent permeability of riluzole.


CONCLUSIONS
Co-administration of ciprofloxacin with riluzole increases the systemic levels of riluzole and thereby the oral pharmacokinetic properties of riluzole while co-administration of grapefruit juice with riluzole has no significant effect.
Pharmacy Department, BITS-Pilani Hyderabad Campus, Hyderabad, Andhra Pradesh, India. rpunnarao@bits-hyderabad.ac.in
Punna Rao
PR
Ravi
Rahul
R
Vats
Upendra Reddy
UR
Kora
D000818:Animals; D019540:Area Under Curve; D001628:Beverages; D002939:Ciprofloxacin / Q000494:pharmacology*; D032083:Citrus paradisi; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D004347:Drug Interactions; D018565:Food-Drug Interactions; D007408:Intestinal Absorption / Q000502:physiology; D008297:Male; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D019782:Riluzole / Q000493:pharmacokinetics*
D065609:Cytochrome P-450 CYP1A2 Inhibitors; D002939:Ciprofloxacin; D019782:Riluzole