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Titolo:
PHARMACOKINETICS AND BIOAVAILABILITY OF MIDAZOLAM AFTER INTRAVENOUS, SUBCUTANEOUS, INTRAPERITONEAL AND ORAL-ADMINISTRATION UNDER A CHRONIC FOOD-LIMITED REGIMEN - RELATING DRL PERFORMANCE TO PHARMACOKINETICS
Autore:
LAU CE; MA F; WANG YX; SMITH C;
Indirizzi:
RUTGERS STATE UNIV,DEPT PSYCHOL,BUSCH CAMPUS NEW BRUNSWICK NJ 08903 FERRIS STATE UNIV,DEPT PHARM PRACTICE BIG RAPIDS MI 00000
Titolo Testata:
Psychopharmacology
fascicolo: 3, volume: 126, anno: 1996,
pagine: 241 - 248
Fonte:
ISI
Lingua:
ENG
Soggetto:
MOTOR CONTROL; RATS; CAFFEINE; BENZODIAZEPINES; RO-15-1788; WITHDRAWAL; MODULATION; TRIAZOLAM; DURATION; BINDING;
Keywords:
BENZODIAZEPINE; BIOAVAILABILITY; DRL; FOOD LIMITATION; MIDAZOLAM; PHARMACOKINETICS; PHARMACODYNAMICS; ROUTE OF ADMINISTRATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Physical, Chemical & Earth Sciences
Physical, Chemical & Earth Sciences
Physical, Chemical & Earth Sciences
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
26
Recensione:
Indirizzi per estratti:
Citazione:
C.E. Lau et al., "PHARMACOKINETICS AND BIOAVAILABILITY OF MIDAZOLAM AFTER INTRAVENOUS, SUBCUTANEOUS, INTRAPERITONEAL AND ORAL-ADMINISTRATION UNDER A CHRONIC FOOD-LIMITED REGIMEN - RELATING DRL PERFORMANCE TO PHARMACOKINETICS", Psychopharmacology, 126(3), 1996, pp. 241-248

Abstract

The effects of midazolam on animal behavior often are evaluated undera chronically food-limited regimen, which is used to implement food-reinforced performance, but the corresponding pharmacokinetics are lacking. The present study investigated the pharmacokinetics of midazolam after IV, SC, IP, and PO administration in food-limited rats. A two-compartment model best described the concentration-time profiles for thefour routes of administration. The rate of midazolam absorption was rapid, and peak concentrations were attained in less than 7 min for thethree extravascular routes. The mean volume of distribution of the central compartment and clearance were 0.77 l/kg and 2.03 l/h per kg, respectively. Midazolam elimination half-lives for the four routes of administration ranged from 23.1 to 49.5 min, and metabolites could not be detected. The mean absolute bioavailability was route-dependent: 39.3% (SC) 19.2% (IP) and 4.6% (PO). The markedly low oral bioavailability found in food-limited rats contrasted to the value reported for free-feeding rats (45%). Although the IP route yielded the highest maximumconcentration on occasion, serum midazolam concentration-time profiles were variable, but did correspond to respective sedative responses. DRL 45-s performance after SC, IP, and PO administration further supported the advisability of using the SC route of administration, as opposed to the IP route, for studying midazolam dose-response relations. The bioavailability values assessed from DRL, performance also agree with the measured pharmacokinetic values.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 18:56:58