Ontogeny of fetal renal organic cation excretion: a study with cimetidine and ranitidine during the latter half of gestation in the pregnant ewe.
The organic cation cimetidine undergoes renal tubular secretion in the near-term ovine fetus. We investigated the ontogeny of renal tubular secretion of organic cations in the fetus from 80 days of gestation (term = 145). Sixteen sheep were administered both cimetidine and ranitidine in random order by a combination of bolus and i.v. infusion to achieve steady-state plasma concentrations of 1000 to 2000 ng/ml. A further two sheep received cimetidine only. Steady-state plasma concentrations were reached within 2 to 3 hr. Creatinine was used as a marker of glomerular filtration rate. Maternal renal clearance of cimetidine (0.51 +/- 0.18 l/min) and ranitidine (0.54 +/- 0.14 l/min) were not correlated with the period of gestation. Cimetidine/creatinine and ranitidine/creatinine renal clearance ratios were higher than unity being 5.48 +/- 1.91 and 5.65 +/- 1.18, respectively. Fetal creatinine renal clearance increased exponentially with gestational age (r2 = 0.577, P less than .001). Fetal renal clearance of both cimetidine and ranitidine also increased exponentially with gestational age, this trend being more clear-cut for cimetidine (r2 = 0.582, P less than .001) than for ranitidine (r2 = 0.254, P = .046). The rates of increase for cimetidine and ranitidine were similar to that for creatinine (P greater than .05). At 80 days, cimetidine/creatinine and ranitidine/creatinine renal clearance ratios (3.0 and 4.4, respectively) were higher than unity and did not increase further during the remainder of gestation. Therefore, the ovine fetus possesses an efficient tubular secretory pathway for organic cations by 80 days of gestation.(ABSTRACT TRUNCATED AT 250 WORDS)
Czuba
M A
MA
Department of Surgery, University of Melbourne, Austin Hospital, Victoria, Australia.
Morgan
D J
DJ
Ching
M S
MS
Mihaly
G W
GW
Hardy
K J
KJ
Smallwood
R A
RA
D000818:Animals; D002927:Cimetidine / Q000097:blood / Q000493:pharmacokinetics*; D005314:Embryonic and Fetal Development / Q000502:physiology; D005260:Female; D005325:Fetal Organ Maturity; D005865:Gestational Age; D007668:Kidney / Q000196:embryology*; D007684:Kidney Tubules / Q000201:enzymology / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D011899:Ranitidine / Q000097:blood / Q000493:pharmacokinetics*; D012756:Sheep
D002927:Cimetidine; D011899:Ranitidine