Pharmacokinetic Studies of Highly Purified Human Prolactin in Normal Human Subjects*

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Abstract
Previous estimates of PRL pharmacokinetics have been made using radioiodinated human PRL (hPRL) infusions or by measuring serum PRL disappearance following prolactinoma resection. The recent purification of hPRL in significant quantities made it possible to measure the clearance and volume of distribution directly. Studies were also carried out to determine absorption and clearance after im injection. In five normal men whose endogenous PRL secretion was suppressed by dopamine, a loading dose of hPRL (70-90 .mu.g) followed by a constant infusion (1.39-2.9 ng/min) produced steady state serum PRL levels of 15.2-25.4 ng/mL by 30-60 min. The calculated mean volume of distribution was 7.3 .+-. 2.9 (.+-. SD) L. The calculated MCR was 71 .+-. 19 mL/min .cntdot. m2, and the calculated production rate was 802 .+-. 377 .mu.g/24 h .cntdot. m2. The plasma disappearance half-life following discontinuation of the infusion was 37 .+-. 10 min. The PRL infusate consisted primarily (75.6%) of a 22.5K dalton species, probably PRL monomer, a component eluting at 45K daltons (16.1% of the total radioimmunoreactivity), probably dimer, and a small amount of a larger mol wt species. Serum obtained during dopamine infusion but before hPRL infusion contained 68.1% of the 22.5K, 7.2% of the 45K, and 24.7% of the larger mol wt moieties. During hPRL infusion in two men there was a relative decrease in the proportion of PRL monomer to 55% and 69% and a relative increase in the PRL dimer to 33% and 18%, respectively. hPRL was injected im in doses of 1, 2, 4, and 8 .mu.g/kg without prior dopamine infusion. No significant changes in serum PRL levels occurred after the 1 and 2 .mu.g/kg doses (n = 5). After the 4 .mu.g/kg dose (n = 8), mean serum PRL levels rose from 10.0 .+-. 1.8 (.+-.SEM) ng/mL to peak levels of 13.1 .+-. 1.8 ng/mL (P < 0.01). After the 8 .mu.g/kg dose (n = 7), PRL levels rose from 9.3 .+-. 1.6 to 16.5 .+-. 1.8 ng/mL (P < 0.01). The PRL rise began between 60 and 80 min after injection, peak levels occurred at 160-180 min. In two men given 8 .mu.g/kg who were sampled for an additional 3 h, PRL levels peaked at 200-220 min and began to fall by 220-240 min, but had not returned to baseline by 6 h. There were no side-effects of PRL administration, although the 8 .mu.g/kg dose caused transient local discomfort. The administration of hPRL produced serum levels within the physiological and pathophysiological ranges. The disappearance t1/2 of the exogenous hPRL was similar to that previously reported for endogenous hPRL, suggesting that degradation of the purified hPRL was not accelerated. The MCR calculated from these studies is slightly greater than that obtained using radioiodinated hPRL in other studies. The volume of distribution of PRL in humans, based on these results, is somewhat greater than the plasma volume.