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Absorption Half-life (absorption + half-life)
Selected AbstractsControlled Transdermal Delivery of Propranolol Using HPMC Matrices: Design and In-vitro and In-vivo EvaluationJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 2 2000P. R. P. VERMA To improve bioavailability and achieve a smoother plasma-concentration profile as compared with oral administration, a matrix-dispersion-type transdermal delivery system was designed and developed for propranolol using different ratios of hydroxypropyl-methylcellulose (HPMC) K4M, K15M and K100M. Formulations were evaluated for in-vitro dissolution characteristics using a Cygnus' sandwich-patch holder. Drug release followed Higuchi rather than zero-order or first-order kinetics. In-vivo evaluation was carried out on healthy volunteers (21 ± 1.41 years; 60.89 ± 5.35 kg) following the balanced incomplete block design. The dissolution rate constant (k) and data generated from plasma and urine (Cmax, maximum plasma concentration; tmax, time to reach peak plasma concentration; AUC, area under the curve; ke, elimination rate constant; t½e, elimination half-life; ka, absorption rate constant; t½a, absorption half-life) were evaluated statistically by two-way analysis of variance. Statistically excellent correlation was found between the percentage of drug absorbed and Cmax, AUC0,24 and AUC0-,. A highly significant difference (P < 0.001) was observed when Cmax and AUC0-, generated from plasma and urine were compared, but ke, t½e, ka and t½a did not differ significantly (P > 0.1). We conclude that urinary excretion data may be used as a simpler alternative to blood level data in studying the kinetics of absorption and deriving the absorption parameters. [source] Pharmacokinetics of cefepime administered by i.v. and i.m. routes to ewesJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2005M. ISMAIL The pharmacokinetics of cefepime were studied following i.v. and i.m. administration of 20 mg/kg in 10 ewes. Following i.v. administration of a single dose, the plasma concentration,time curves of cefepime were best fitted using a two-compartment open model. The elimination half-life (t1/2,) was 1.76 ± 0.07 h, volume of distribution at steady-state [Vd(ss)] was 0.32 ± 0.01 L/kg and total body clearance (ClB) was 2.37 ± 0.05 mL/min·kg. Following i.m. administration, the drug was rapidly absorbed with an absorption half-life (t1/2ab) of 0.49 ± 0.05 h, maximum plasma concentration (Cmax) of 31.9 ± 1.5 ,g/mL was attained at (tmax) 1.1 ± 0.2 h and the drug was eliminated with an elimination half-life (t1/2el) of 2.06 ± 0.11 h. The systemic bioavailability (F) after i.m. administration of cefepime was 86.8 ± 7.5%. The extent of plasma protein binding measured in vitro was 14.8 ± 0.54%. The drug was detected in urine for 36 h postadministration by both routes. [source] Pharmacokinetics and analgesic effects of intravenous propacetamol vs rectal paracetamol in children after major craniofacial surgeryPEDIATRIC ANESTHESIA, Issue 7 2008SANDRA A. PRINS MD PhD Summary Background:, The pharmacokinetics and analgesic effects of intravenous and rectal paracetamol were compared in nonventilated infants after craniofacial surgery in a double-blind placebo controlled study. Methods:, During surgery all infants (6 months,2 years) received a rectal loading dose of 40 mg·kg,1 paracetamol 2 h before anticipated extubation. On admittance to the pediatric surgical ICU, the children were randomized to receive either a 15 min intravenous infusion of 40 mg·kg,1 propacetamol, a prodrug of paracetamol, or 20 mg·kg,1 paracetamol rectally every 6 h. A population pharmacokinetic analysis of the paracetamol plasma concentration time-profiles was undertaken using nonlinear mixed effects models. The visual analogue scale (VAS) (score 0,10 cm) and COMFORT Behavior scale (score 6,30) were used to monitor analgesia in the 24-h period following surgery. Results:, Twelve infants received intravenous propacetamol and 14 paracetamol suppositories. Paracetamol pharmacokinetics were described according to a two-compartmental model with linear disposition. Pharmacokinetic parameters were standardized to a 70 kg person using allometric ,1/4 power' models. Parameter estimates were: absorption half-life from the rectum 4.6 h, propacetamol hydrolysis half-life 0.028 h, clearance 12 l·h,1·70 kg,1, intercompartmental clearance 116 l·h,1·70 kg,1, central and peripheral volume of distribution 7.9 and 44 l·70 kg,1, respectively. During the 24-h study period 22 infants exhibited VAS scores <4 cm, which was considered a cutoff point. On single occasions four patients, two in each group, exhibited a VAS score ,4 cm. Nine patients in the rectal treatment group and three patients in the intravenous treatment group received midazolam for COMFORT-B scores exceeding 17 (P < 0.05). Conclusions:, Intravenous propacetamol proved to be more effective than rectal paracetamol in infants after craniofacial surgery. Midazolam was more frequently administered to patients receiving paracetamol suppositories, indicating that these children experienced more distress, possibly caused by pain. [source] Pharmacokinetics and tissue residues of marbofloxacin in crucian carp (Carassius auratus) after oral administrationAQUACULTURE RESEARCH, Issue 6 2009Yanlei Zhu Abstract Pharmacokinetics and residue elimination of marbofloxacin (MBF) were studied in crucian carp (Carassius auratus, 250±30 g) kept at two water temperatures of 15 and 25 °C. Marbofloxacin concentrations in plasma and tissues were analysed by means of high-performance liquid chromatography using an ultraviolet detector. The limits of detection were 0.02 ,g mL,1, 0.02 ,g g,1, 0.025 ,g g,1, 0.02 ,g g,1 and 0.025 ,g g,1 in plasma and muscle, skin, liver and kidney respectively. Fish were administered orally at a single dosage of 10 mg kg,1 body weight in the PK group. The data were fitted to two-compartment open models at both temperatures. At 15 °C, the absorption half-life () and distribution half-life (t1/2,) of the drug were 0.36 and 4.48 h respectively. The corresponding values at 25 °C were 0.23 and 0.87 h respectively. The elimination half-life (t1/2,) was 50.75 h at 15 °C and 25.05 h at 25 °C. The maximum MBF concentration (Cmax) differed little between 15 (6.43 ,g mL,1) and 25 °C (8.36 ,g mL,1). The time to peak concentration was 1.74 h at 15 °C and 0.78 h at 25 °C. The apparent volume of distribution (Vd/F) of MBF was estimated to be 1.36 and 0.87 L kg,1 at 15 and 25 °C respectively. The area under the concentration,time curve (AUC) was 301.80 ,g mL,1 h at 15 °C and 182.80 ,g mL,1 h at 25 °C. The total clearance of MBF was computed as 0.03 and 0.05 L h,1 kg,1 at 15 and 25 °C respectively. After repeated oral administration at a dosage of 10 mg kg,1 body weight per day for 3 days, the results showed that the elimination half-lives () of MBF from all tissues at 15 °C were longer than that at 25 °C. Therefore, water temperature is an important factor to be considered when deciding a reasonable withdrawal time. [source] The effect of tamoxifen on the pharmacokinetics of letrozole in female ratsBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 7 2006X. Tao Abstract The effects of single doses of tamoxifen (TAM; 0.5,5 mg/kg, i.v.) and chronic pretreatment with TAM (0.1,5.0 mg/kg/day, i.p. for 7 consecutive days) on letrozole (0.5 mg/kg, i.v.) pharmacokinetics were evaluated in female Sprague-Dawley rats. The plasma concentration-time profiles of letrozole (0.1,2.0 mg/kg) after single i.v. doses were analysed by the non-compartment model with terminal half-lives (t1/2,,z) ranging from 34.3 to 37.5 h. The volume of distribution at the terminal phases (Vd(,z)) ranged from 1.9 to 2.1 l/kg and clearance (CL) varied from 0.036 to 0.042 l/(h·kg). After co-administration of TAM and letrozole intravenously, the t1/2, Vd(,z) and CL of letrozole were not significantly altered. Chronic pretreatment with TAM significantly decreased the t1/2 of letrozole by about 33%, and increased its clearance by an average of 40%. However, TAM pretreatment did not significantly affect the Vd((,z) of letrozole in female rats. Co-administration of letrozole and TAM orally increased the absorption half-life of letrozole threefold although the absolute bioavailability remained unchanged. These observations suggest that single oral doses of TAM delay the absorption of letrozole while chronic pretreatment with TAM accelerates the elimination of letrozole, probably due to induction of cytochrome P450 enzymes in rats. Copyright © 2006 John Wiley & Sons, Ltd. [source] | ||||||||||