Resting human muscle blood flow (MBF) was determined simultaneously in the usual intramuscular injection sites to resolve whether variance in MBF could account for differences in drug absorption. Three pairs of muscles (gluteus maximus, vastus lateralis, and deltoid) were studied in each of 20 adult subjects. Use of dual, matched linear rate meters allowed two muscles to be studied simultaneously, with the order of injection random within an incomplete block design. MBF was calculated from the 133xenon washout rate using a single exponential that the computer found to best fit the data. Deltoid MBF (11.6 ml/100 gm/min plus or minus 0.5) was significantly (p smaller than 0.05) greater than gluteus MBF (9.6 plus or minus 0.5), with vastus or between right and left sides for each muscle. These data indicate that there are consistent differencies in resting MBF among specific muscle groups of sufficient magnitude (19%) to affect the rate of absorption and peak serum levels following intramuscular administration of drugs.

Five women with premature ovarian failure were studied in a randomized cross-over design to compare the biochemical effects of transdermal to oral estradiol administration when used in doses appropriate for endometrial preparation in a donor oocyte program. Patients randomly received increasing dosages of oral micronized or transdermal estradiol for 4 week, with progesterone added in the last 2 weeks, to mimic a normal hormonal cycle. Serum samples were assayed throughout treatment and compared to those from normally cycling premenopausal controls. In general, serum estradiol remained within the normal range in both treatment groups, whereas peak serum estrone levels were 10-fold higher in the orally treated group than those in the transdermally treated group. Serum levels of sex hormone-binding globulin, thyroid binding globulin, and renin substrate were all significantly elevated by day 14 in the orally treated patients and unchanged in the transdermal subjects. While plasminogen was unaltered by either route of administration, antithrombin-III levels fell with both treatments. Changes in gonadotropin levels were similar in both groups, with suppression of FSH by the end of the simulated cycles, but not into the normal premenopausal range. In conclusion, both estrogen replacement regimens provided near-normal serum estradiol profiles. However, despite the relatively high doses necessary to mimic a hormonally normal cycle, the transdermal route did not significantly alter the hepatic parameters studied, suggesting that this route of administration may have less adverse hepatic effects.

Diabetic patients manifest increased vascular permeability. To determine whether insulin per se might increase vascular permeability, five nondiabetic men were studied by the hyperinsulinemic-euglycemic clamp technique. Each subject received a 0.72-nmol/kg body wt i.v. insulin bolus, followed by a 72-pmol.kg-1.min-1 insulin infusion for 4 h. Euglycemia was maintained by the Biostator glucose controller. At 7 h of study, 10 microCi i.v. 125I-labeled albumin was injected as bolus dose. Frequent blood samples were drawn during the next 70 min for determination of the transcapillary escape rate (TER) of albumin. Subjects returned 1-2 wk later for a control study, during which 0.45% saline was infused at a rate identical to the dextrose and insulin infusion rates during the hyperinsulinemic clamp. The mean +/- SE serum insulin levels during the hyperinsulinemic clamp and saline infusion were 9786 +/- 126 and 46 +/- 4 pM, respectively, whereas serum glucose during the two sessions was similar (5.0 +/- 0.2 vs. 4.8 +/- 0.1 mM, NS). Identical fluid volumes were infused during the two sessions (1767 +/- 197 ml/7 h), and urine outputs did not differ significantly (1615 +/- 309 vs. 1035 +/- 248 ml/7 h). The TER of albumin was greater in all five men after hyperinsulinemia than after saline infusion (18.3 +/- 2.7 vs. -2.8 +/- 2.3%/h, P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)