Pentachlorophenol toxicokinetics after intravenous and oral administration to rat.
1. The toxicokinetics of pentachlorophenol (PCP) were studied in rats. Doses of 2.5 mg/kg were given i.v. (bolus, five rats) and orally (gastric intubation, five rats). Concentrations in plasma, urine and faeces were measured by capillary g.l.c. with electron-capture detection. 2. After i.v. administration, the clearance and volume of distribution at steady state were 0.026 +/- 0.003 l/h per kg and 0.25 +/- 0.02 l/kg, respectively. These two parameters exhibit low inter-rat variability (coefficients of variation less than 15%). The half-life of the initial decline of PCP plasma concn. was less than 1.3 h, while the second phase half-life was 7.11 +/- 0.87 h. 3. After oral administration the peak plasma concn. (7.3 +/- 2.8 micrograms/ml) occurred between 1.5 and 2 h and absorption was complete (bioavailability = 0.91-0.97). No distinct distribution phase was observed and the elimination half-life was 7.54 +/- 0.44 h. 4. PCP clearance is essentially metabolic since only 5.3 +/- 0.2% dose is eliminated unchanged by the kidney. About 60% dose was recovered in urine, mainly as conjugated PCP and conjugated tetrachlorohydroquinone (TCHQ). 5. For both routes of administration, about 10% dose was recovered in faeces as PCP and/or metabolites, which indicates that biliary excretion contributes to total elimination.
Reigner
B G
BG
Department of Pharmacy, University of California, San Francisco 94143-0446.
Gungon
R A
RA
Hoag
M K
MK
Tozer
T N
TN
D000042:Absorption; D000284:Administration, Oral; D000818:Animals; D006207:Half-Life; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D010416:Pentachlorophenol / Q000493:pharmacokinetics* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains
D010416:Pentachlorophenol