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Terminal Elimination Half-life (terminal + elimination_half-life)

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Medical Sciences	100%

Selected Abstracts

Pharmacokinetic profile and behavioral effects of gabapentin in the horse

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2010
R. L. TERRY
Terry, R. L., McDonnell, S. M., van Eps, A. W., Soma, L. R., Liu, Y., Uboh, C. E., Moate, P. J., Driessen, B. Pharmacokinetic profile and behavioral effects of gabapentin in the horse. J. vet. Pharmacol. Therap. 33, 485,494. Gabapentin is being used in horses although its pharmacokinetic (PK) profile, pharmacodynamic (PD) effects and safety in the equine are not fully investigated. Therefore, we characterized PKs and cardiovascular and behavioral effects of gabapentin in horses. Gabapentin (20 mg/kg) was administered i.v. or p.o. to six horses using a randomized crossover design. Plasma gabapentin concentrations were measured in samples collected 0,48 h postadministration employing liquid chromatography-tandem mass spectrometry. Blood pressures, ECG, and sedation scores were recorded before and for 12 h after gabapentin dosage. Nineteen quantitative measures of behaviors were evaluated. After i.v. gabapentin, the decline in plasma drug concentration over time was best described by a 3-compartment mammillary model. Terminal elimination half-life (t1/2,) was 8.5 (7.1,13.3) h. After p.o. gabapentin terminal elimination half-life () was 7.7 (6.7,11.9) h. The mean oral bioavailability of gabapentin (±SD) was 16.2 ± 2.8% indicating relatively poor absorption of gabapentin following oral administration in horses. Gabapentin caused a significant increase in sedation scores for 1 h after i.v. dose only (P < 0.05). Among behaviors, drinking frequency was greater and standing rest duration was lower with i.v. gabapentin (P < 0.05). Horses tolerated both i.v. and p.o. gabapentin doses well. There were no significant differences in and . Oral administration yielded much lower plasma concentrations because of low bioavailability. [source]

Clinical Pharmacokinetics of Frovatriptan

HEADACHE, Issue 2002
P. Buchan PhD
Objective.,To review available data on the clinical pharmacokinetics of frovatriptan. Background.,Preclinical data suggest that the pharmacokinetic profile of frovatriptan may differ from that of the currently available triptans. Methods.,Studies of healthy volunteers, subjects with renal or hepatic impairment, elderly subjects, and patients with migraine during and between attacks were reviewed. Results.,Oral bioavailability of frovatriptan is 22% to 30%, and although the time to maximum concentration is typically 2 to 3 hours, approximately 60% to 70% of plasma maximum concentration is achieved within 1 hour of dosing. Frovatriptan distributes into erythrocytes, with binding reversible and time dependent. The relatively long terminal elimination half-life (about 26 hours) confers good systemic exposure and may produce a long duration of therapeutic action, thus reducing migraine recurrence and the need for redosing. Systemic exposure to frovatriptan generally correlates with dose between 1 and 100 mg. Blood and plasma frovatriptan concentrations are consistently higher in females, but there is no need to adjust dose according to gender. Pharmacokinetics are essentially unaffected by food and were predictable after repeat dosing; steady state is approached in about 4 to 5 days. Pharmacokinetics were changed only slightly in subjects with renal impairment or mild-to-moderate hepatic impairment, elderly individuals, and during migraine attacks. Frovatriptan is principally metabolized by the CYP1A2 isoenzyme of cytochrome P-450 and is cleared by the kidney and liver, each having sufficient capacity to compensate for impairment of the other. Conclusions.,Frovatriptan can be taken without regard for food intake, and because of the large therapeutic margin and shallow dose-response curve, there is no need for dosage adjustment in the elderly, in women taking a combined oral contraceptive, in patients with mild-to-severe renal impairment, mild-to-moderate hepatic impairment, or according to gender. The long duration of exposure may reduce the likelihood of early migraine recurrence. [source]

Clinical Efficacy of Frovatriptan: Placebo-Controlled Studies

HEADACHE, Issue 2002
R. Ryan MD
Objective.,To confirm the clinical efficacy of frovatriptan 2.5 mg. Background.,Frovatriptan is a new 5-hydroxytryptamine (5-HT)1B/1D receptor agonist being developed for the acute treatment of migraine with or without aura. Results from preclinical and clinical pharmacology studies showed frovatriptan to be a potent 5-HT1B receptor agonist with a long terminal elimination half-life (26 hours) and a broad therapeutic index. Design.,Three randomized, placebo-controlled, double-blind, parallel-group trials, in a total of 2676 patients, were performed to confirm the clinical efficacy of frovatriptan 2.5 mg for the acute treatment of migraine. Results.,In all three studies, headache response 2 hours after frovatriptan dosing was significantly greater than that seen with placebo (P.001) with approximately a two-fold measure of effect over placebo for headache response at 2 and 4 hours postdosing. Time to headache response occurred within 1.5 hours in a substantial proportion of patients. The incidence of 24-hour headache recurrence with frovatriptan was low (10% to 25%). Frovatriptan therapy also was associated with a high degree of patient satisfaction. Conclusions.,Frovatriptan represents a consistently effective acute treatment for migraine and accompanying symptoms. [source]

Pharmacokinetic profile and behavioral effects of gabapentin in the horse

In vivo release of oxytetracycline from a biodegradable controlled-release gel injected subcutaneously in Japanese quail (Coturnix coturnix japonica)

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2003
L. A. Tell
A long-acting, biodegradable, controlled-release formulation of oxytetracycline (CR-OTC) was evaluated in 18 adult Japanese quail (Coturnix coturnix japonica) following a single subcutaneous (s.c.) injection. Prior to characterizing the release of oxytetracycline (OTC) from the CR-OTC, the pharmacokinetic parameters of intravenously (i.v.) administered OTC were determined. Concentrations of free OTC were measured using a bioassay. The plasma concentration,time profile of OTC after a single i.v. injection at 20 mg/kg was best fit to an open two-compartmental model, with the following pharmacokinetic parameters: area under the curve (AUC) = 36.72 mg · h/L, terminal elimination half-life = 2.34 h, clearance (Cl) = 0.545 L/kg/h. Plasma [OTC] was >1.0 ,g/mL for at least 4 h following i.v. injection. The CR-OTC gel was well tolerated at a dosage of 1500 mg/kg s.c. Plasma [OTC] rose to >1.0 ,g/mL within 24 h; it remained >1.0 ,g/mL for at least 10 days in all birds sampled at that time point (n = 9) and for at least 18 days in two of nine birds. Using a deconvolution technique, it was determined that approximately 54.8% of the administered OTC was released from the CR-OTC over the 45-day observation period. This long-acting, biodegradable controlled-release OTC formulation may have potential for the treatment of chlamydophila infections and other OTC-sensitive bacteria in Japanese quail, however further studies are necessary to determine its safety and clinical application. [source]

Pharmacokinetics and tissue distribution of the anticholinergics tiotropium and ipratropium in the rat and dog

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 5 2001
A. Leusch
Abstract Ipratropium, a current treatment for chronic obstructive pulmonary disease (COPD) and tiotropium, a longer acting anticholinergic bronchodilator currently being developed for COPD are structurally related to atropine. In this study, the intravenous (i.v.), oral (p.o.) and intratracheal (i.tr.) single dose pharmacokinetics (PK) of tiotropium and ipratropium were determined in rat and dog. In rats, concentration,time profiles of tiotropium and ipratropium after single i.v. bolus administration of 7,8 mg kg,1 are similar. Both drugs are highly cleared (Cl between 87 and 150 ml min,1 kg,1) and extensively distributed into tissues (volume of distribution Vss between 3 and 15 l kg,1). In dogs, this holds also true for both drugs (Cl between 34 and 42 ml min,1 kg,1, Vss between 2 and 10 l kg,1), although different dose regimen were applied (i.v. bolus of 0.08 mg kg,1 vs. infusion of 0.1 mg kg,1 h,1 for 3 h). Tiotropium plasma concentrations increased linearly in rats over a wide dose range following single i.v. administration. Both ipratropium and tiotropium showed a comparable terminal elimination half-life in rat urine (21,24 h) after single i.v. administration, which was much longer than the corresponding half-life in plasma (6,8 h). Whole body autoradiography in rats revealed a broad and rapid tissue distribution of [14C]tiotropium radioactivity after single i.v. administration. A comparable distribution pattern has also been reported earlier for ipratropium. Copyright © 2001 John Wiley & Sons, Ltd. [source]