Transplacental and mammary passage of radioactivity in rats treated vaginally and orally with (/sup 14/C)propranolol
Single doses (10 mg/kg) of an aqueous solution of (14C)propranolol were administered either orally (po) or intravaginally (ivg) on gestational d 15, or on postpartum d 7-10. Upon ivg administration, (14C)propranolol was quickly transferred to systemic circulation and the mean blood (14C) concentrations were significantly greater during the first 0.25-2 h than in po dosed counterparts. About 98% of the ivg applied dose was absorbed after 6 h in gravid rats, and the combined 6-h excretions of radioactivity in the urine (ivg = 24.6%; po = 22.9%) and feces (ivg = 16.8%; po = 14.6%) were equivalent in both groups. At the end of 6 h, the levels of (14C) in the urinary bladder, adrenal, uterus, ovary, spleen, skeletal muscle, brain, heart, lung and fat were significantly higher in ivg treated rats than po dosed animals. Compared with the maternal plasma (ivg = 0.76; po = 0.88 microgram/ml), the mean concentrations of (14C) in the placentas were similar in both groups, while the amounts of (14C) were three to five times lower in the amniotic fluids and the fetuses of both po and ivg treated dams. In lactating rats, over 99% of the administered radioactivity was absorbed from the vagina within 6 h. The blood concentrations of (14C) were significantly elevated at 0.5 and 1 h in the per vaginam treated animals, and afterward the disappearance rate of (14C) followed a similar course in both groups. Following ivg application, the milk radioactivity peaked at 0.5 h and declined rapidly. However, the appearance of (14C) in milk was rather slow after oral dosing: the milk (14C) peaked between 2 and 3 h posttreatment and remained steady thereafter. The milk to blood (M/B) (14C) concentration ratios were markedly greater during 0.5 to 1 h in the ivg group than in their po dosed counterparts.
- Research Organization:
- Drug Toxicology Division, Health and Welfare Canada, Ottawa
- OSTI ID:
- 6971740
- Journal Information:
- J. Toxicol. Environ. Health; (United States), Vol. 24:1
- Country of Publication:
- United States
- Language:
- English
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PROPANOLS
MEMBRANE TRANSPORT
TISSUE DISTRIBUTION
ABSORPTION
AMNIOTIC FLUID
CARBON 14 COMPOUNDS
MILK
ORAL ADMINISTRATION
PLACENTA
PREGNANCY
RATS
SCINTILLATION COUNTING
TRACER TECHNIQUES
ALCOHOLS
ANIMALS
BIOLOGICAL MATERIALS
BODY FLUIDS
COUNTING TECHNIQUES
DISTRIBUTION
FETAL MEMBRANES
FOOD
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MATERIALS
MEMBRANES
ORGANIC COMPOUNDS
RODENTS
VERTEBRATES
551001* - Physiological Systems- Tracer Techniques