Factors determining human chorion laeve permeability in vitro

Abstract

An increased mean diffusion permeability across human chorion laeve in vitro was measured for meperidine (D = 5.26 × 10−6 cm.2 sec.−1) and diazepam (D = 4.51 × 10−6 cm.2 sec.−1). These values corresponded to large chloroform-buffer partition coefficients (49 and 29) measured for these two compounds. Diffusion permeability values of 3.98 and 2.18 × 10−6 cm.2 sec.−1 measured for urea and glucose corresponded to their relative insolubility in lipid, as indicated by chloroform-buffer partition coefficients of 0.05 and 0.004, respectively. An increase in placental permeability in vitro to the weak organic acid 5,5-dimethyl, 2,4-oxazalidinedione at lower pH's corresponded to an increase in the fat-soluble nonionized fraction of this compound. These data support the concept that this tissue is most permeable to compounds of relatively small molecular size and/or with a high level of lipid solubility. The large diffusion permeability values measured for meperidine and diazepam suggest that these compounds will diffuse rapidly between mother and fetus at a maximal rate limited only by uterine blood flow.