Bioequivalence study of a fixed dose combination of nitazoxanide and ofloxacin in Indian healthy volunteers.
OBJECTIVE
The pharmacokinetics of nitazoxanide (CAS 55981-09-4) and ofloxacin (CAS 82419-36-1) has been extensively evaluated in adult human volunteers individually after oral administration of tablet formulation. However, no published data is available regarding the combined pharmacokinetics and bioavailability of this particular fixed dose combination. In light of the above, a clinical study was designed to evaluate the bioequivalence of two fixed dose combination (FDC) products of two manufacturers containing nitazoxanide 500 mg and ofloxacin 200 mg in healthy Indian male volunteers.


METHODS
24 healthy male volunteers (age 25 +/- 4.6 years; weight 74.5 +/- 7.87 kg) were enrolled in this study. Each subject received a Test fixed dose combination and a Reference fixed dose combination formulation in a randomized, single dose, fasting state, two period, crossover study design with a 1-week washout period between the doses. Extraction of the drugs from the plasma was carried out by precipitation method. Analysis of tizoxanide (active metabolite of nitazoxanide) and ofloxacin from plasma samples was done by a simple and sensitive HPLC method using UV detection developed in our laboratory. An analysis of variance was performed on the pharmacokinetic parameters Cmax, AUC(0-t), AUC(0-infinity). using general linear model (GLM) procedures in which sources of variation were subject, formulation, period.


RESULTS
The results of this investigation indicated that there were no statistically significant differences between the two products in either the mean concentration-time profiles or in the obtained pharmacokinetic parameters. 90 % confidence limits for the log-transformed data of Cmax, AUC(0-t), AUC(0-infinity) were within the acceptable range of 0.80-1.25.


CONCLUSIONS
Thus, these findings clearly indicate that the two products are bioequivalent in terms of rate and extent of drug absorption. Both the preparations were well tolerated with no adverse reactions seen throughout the study.
Agarwal
Sangita
S
Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
Solomon
W D Sam
WD
Gowda
K Veeran
KV
Selvan
P Senthamil
PS
Ghosh
Debotri
D
Sarkar
Amlan Kanti
AK
Chattaraj
Tapas Kumar
TK
Pal
Tapan Kumar
TK
D000328:Adult; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004338:Drug Combinations; D006207:Half-Life; D006801:Humans; D008297:Male; D009574:Nitro Compounds; D015242:Ofloxacin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013056:Spectrophotometry, Ultraviolet; D013607:Tablets; D013810:Therapeutic Equivalency; D013844:Thiazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000890:Anti-Infective Agents; D004338:Drug Combinations; D009574:Nitro Compounds; D013607:Tablets; D013844:Thiazoles; D015242:Ofloxacin; C041747:nitazoxanide