title: Report: pharmacokinetic and drug interaction studies of pefloxacin with paracetamol (NNAID) in healthy volunteers in Pakistan.
abstract: In the present study, the pharmacokinetic and drug interaction evaluation of two drugs pefloxacin and paracetamol was carried out by a single-dose, two-treatment and two-sequence crossover design. Total fifteen healthy volunteers participated out of which ten completed the study. All were male volunteers, aged 22.36 years (means), with a mean weight of 76.45±12.05 Kg. The washout period between treatments was 5 week. Initially the method utilized for quantitative analysis of the drug was developed which was further validated. The study involved plasma protein precipitation with ethyl acetate and detection was done at 275nm. The retention time for pefloxacin 18±1 min and paracetamol were approximately 6±1 min, respectively. The calibration curve for pefloxacin was linear in the concentration range of 0.125-12.0mg/ml with r(2)=0.9987 in plasma. Standard concentration solution was maintained on the same temperature as that of volunteer's samples to optimize the periods for the determination of drug concentration in the plasma samples. Blood samples were collected from volunteers at different time intervals. The pharmacokinetics and drug interaction studies were anticipated by plotting concentration versus time-profiles. The value of AUC0-∞ in control was 67.355±3.174μg.h/ml, in treatment 61.242±3.868μg.h/ml along with relative bioavailability =91.395±4.864. Under the control and treatment condition the mean maximum plasma concentrations were found to be 4.679±0.248 μg/ml and 4.6595±0.266 μg/ml respectively. The average T(max) for plasma concentrations was 1.819±0.1743hr and 1.605 ±0.1134hr respectively. The biological half-lives in the two phases of studies were found to be 7.953±0.33hr in control and 7.7257±0.355hr in treatment. No significant effect were observed on the bioavailability and pharmacokinetics of pefloxacin by the concomitant administration with paracetamol, however very minor effect were observed that might be related with inter-individual variation in human volunteers. This pharmacokinetic studies also indicated that the level of drug (Cmax) do not differ from previous studies in different races.
authors.affiliation: College of Pharmaceutical Sciences, RAK Medical and Health Sciences University, Ras Al Khaimah, UAE.
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Gauhar
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, University of Karachi, Pakistan.
authors.forename: Syed Ayub
authors.initials: SA
authors.lastname: Ali
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, University of Karachi, Pakistan.
authors.forename: Syed Baqir
authors.initials: SB
authors.lastname: Naqvi
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, University of Karachi, Pakistan.
authors.forename: Muhammad Harris
authors.initials: MH
authors.lastname: Shoaib
mesh_terms: D000082:Acetaminophen / Q000493:pharmacokinetics* / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000493:pharmacokinetics / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004347:Drug Interactions; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D007202:Indicators and Reagents; D008297:Male; D015366:Pefloxacin / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D012015:Reference Standards; D055815:Young Adult
chemical_list: D018712:Analgesics, Non-Narcotic; D000890:Anti-Infective Agents; D007202:Indicators and Reagents; D015366:Pefloxacin; D000082:Acetaminophen