Linked Life Data

2038745

Source:http://linkedlifedata.com/resource/pubmed/id/2038745

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1991-7-1
pubmed:abstractText
The rabbit was utilized for examining the pharmacokinetics of three compounds (acetaminophen, AC; antipyrine, AN; and salicylic acid, SA) in nursing adults and their suckling offspring and for assessing the ability of a diffusional model to predict milk to serum drug concentration ratios (M/S) from in vitro experiments. AC, AN, and SA serum concentration time profiles declined monoexponentially for both adults and their pups. The mean systemic clearance (Cls) for AC in the adults and pups was 16.1 and 13.7 ml/min/kg, respectively. The mean half-lives of AC (t1/2) were 25.5 and 33.3 min in the adult and pup groups, respectively. AN declined in parallel for adult rabbits and an older group of suckling pups (23-25 days old). In a younger group of pups (18-21 days old) it declined with a longer t1/2 (97.5, 95.1, and 347.6 min in the adults, older pups, and younger pups, respectively). The mean AN Cls in the adults, the older pups, and the younger pups was 5.34, 6.30, and 1.91 ml/min/kg, respectively. The time course of SA was prolonged in the suckling pups (t1/2 of 633 min in the pups vs 78.7 min in the adult). The mean Cls values in the adults and the pups were 1.05 and 0.27 ml/min/kg, respectively. The mean systemic clearance of unbound drug (Clu) for SA was 11.2 ml/min/kg in the adults and 0.92 ml/min/kg in the pups. The serum protein binding of AC and AN was limited, whereas the mean free fraction for SA was 9.7% in adult serum and 32.5% in pup serum. AC and AN in milk paralleled serum drug profiles; a time lag was noted for milk SA. M/S ratios were determined in vivo (M/Sobs; AN = 0.885, AC = 0.580, and SA = 0.125) using area under the milk and serum concentration time profiles. Predicted M/S values (M/Spred; AN = 0.779, AC = 0.578, and SA = 0.085) were calculated from in vitro measurements of the unbound fractions of drug in skim milk and serum, the skim to whole milk drug concentration ratio, milk and serum pH, and the pKa of the model compound. Mean values for M/Sobs were highly correlated with M/Spred values (r2 = 0.976) when the present data were combined with previous data for propranolol, phenobarbital, phenytoin, and diazepam (Fleishaker, J.C., and McNamara, P.J., J. Pharmacol. Exp. Ther. 244, 919, 1988). These results support the usefulness of the diffusional model for predicting M/S in vivo, provided that the distributional process is governed by passive diffusion.(ABSTRACT TRUNCATED AT 400 WORDS)
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0041-008X
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
109
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
149-60
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
Pharmacokinetics of acetaminophen, antipyrine, and salicylic acid in the lactating and nursing rabbit, with model predictions of milk to serum concentration ratios and neonatal dose.
pubmed:affiliation
Division of Pharmacology and Experimental Therapeutics, College of Pharmacy, University of Kentucky, Lexington 40536.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.