A modified technique for the sagittal split osteotomy.
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Humans↗
Biomedical subjects
D Max
Publications and source records attributed to D Max.
Single-dose pharmacokinetics of leuprolide in humans following intravenous and subcutaneous administration.
A group of six normal adult male volunteers was divided into two groups (I and II) who received bolus intravenous and subcutaneous 1-mg doses of leuprolide. The study was of a randomized, complete-crossover design. Blood was collected from 0 to 48 h postdosing, and plasma was analyzed for leuprolide using a radioimmunoassay procedure. The data from the intravenous doses were fitted to a two-compartment open model with elimination from the central compartment, assuming a bolus (instantaneous) injection. The data from the subcutaneous doses were fitted to a two-compartment open model with elimination from the central compartment and first-order (monoexponential) absorption from the injection site. Statistical moments were also calculated for both sets of data. The mean beta half-life after the intravenous dosings was 2.9 h and after the subcutaneous dosings was 3.6 h. The difference between these two values, as well as those for plasma clearance, variance in residence time, and volume of distribution at steady state was not statistically significant; however, the differences between the mean values of k21, k12, kel, apparent volume of distribution of the central compartment, mean residence time, and area under the moment curve for the routes of administration were significant (p less than 0.05). The mean residence time following the intravenous dosings averaged 3.1 h and following the subcutaneous dosings averaged 4.3 h, indicating an average mean residence time at the subcutaneous injection site of 1.2 h. The mean volume of distribution at steady state from the intravenous and subcutaneous doses were 26.5 and 37.1 L, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Treatment of breast cancer with gonadotropin-releasing hormone.
Analogs of GnRH, given chronically in a continuous fashion, produce a paradoxic inhibition of pituitary gonadotropin secretion and, consequently, gonadal steroidogenesis. Thus, GnRH analogs are an attractive class of compounds for achieving a medical castration in the treatment of hormone-dependent neoplasms. In a group of 25 premenopausal patients with progressive advanced breast cancer, daily sc administration of 1-10 mg Leuprolide [D-Leu6-Pro9GnRH ethylamide (NEt)] induced objective tumor regression in 44% with a median duration of 9 months. All women treated for at least 10 weeks developed amenorrhea. Profound suppression of gonadotropins, estradiol, and progesterone secretion occurred in all patients on chronic therapy and persisted for the whole treatment period. These effects on tumor growth and ovarian hormone levels are similar to those observed after surgical ovariectomy. Other GnRH analogs such as Buserelin and Zoladex have been found to have similar antitumor and hormonal effects which are also comparable to those produced by surgical ovariectomy. The mode of drug administration is important. Consistent suppression of ovarian function has only been observed with sc injections of the analogs. Chronic intranasal therapy has been found to induce an incomplete suppression of ovarian function in most patients, probably as a result of the poor absorption of these compounds through this route (approximately 2%). Treatment of metastatic breast cancer with GnRH analogs has been associated with remarkable absence of significant toxicity. Despite some evidence in favor of a direct antitumor effect independent of suppression of ovarian function, the use of GnRH analogs in the therapy of advanced breast cancer should be restricted to premenopausal women.
Adult↗
Effect of very high dose D-leucine6-gonadotropin-releasing hormone proethylamide on the hypothalamic-pituitary testicular axis in patients with prostatic cancer.
Potent synthetic analogs of gonadotropin-releasing hormone produce parodoxical antireproductive effects when administered chronically. These compounds are minimally toxic and may exhibit no plateau of the dose-response curve even at very high doses. These considerations served as the basis for our systematic evaluation of [D-leucine6-desarginine-glycine-NH2(10)]gonadotropin-releasing hormone (GnRH-A) proethylamide in the very high dose range (i.e., 10-fold larger amounts than previously used). In rats given the analog for 12 wk, prostate, testis, and seminal vesicle weights were suppressed to a greater extent with 200 micrograms q.d. than with 40 micrograms q.d. (P less than 0.01 prostate, less than 0.01 testis, less than 0.01 seminal vesicles), indicating dose-response effects in the very high dose range. 200 micrograms of [D-Leu6-des-Gly-NH2(10]-GnRH-A consistently suppressed leutinizing hormone (LH) values at 6 and 12 wk (basal 71 +/- 9.5; 6 wk 34 +/- 3.8; 12 wk 28 +/- 5 ng/ml) whereas 40 micrograms suppressed LH variably (basal 33 +/- 3.8; 6 wk 17 +/- 3.9; 12 wk 32 +/- 5.2). Testosterone fell to 15 +/- 2.4 and 19 +/- 2.0 ng/100 ml in response to 200 micrograms q.d. and to 27 +/- 6.4 and 22 +/- 7.4 ng/100 ml with the 40-micrograms dose. These findings in the rodent prompted treatment of stage D prostate cancer patients with similarly high doses of [D-Leu6-des-Gly-NH2(10)]-GnRH-A. After treatment for 11 wk with 1,000 or 10,000 micrograms/d of the analog, testosterone and dihydrotestosterone levels transiently rose and then fell into the surgically castrate range (testosterone 19 +/- 4.4 ng/100 ml [D-Leu6-des-Gly-NH2(10)]-GnRH-A vs. surgically castrate 11 +/- 0.9 ng/100 ml, P = NS; dihydrotestosterone 15 +/- 1.7 ng/100 ml GnRH-A vs. surgically castrate 15 +/- 4.1 ng/100 ml. P = NS). However, unlike the chronic stimulatory effect on the pituitary at lower doses, very high dose therapy resulted in profound suppression of plasma and urine LH. Plasma levels fell to the limit of assay detectability, whereas the more sensitive urinary assay detected prepubertal levels of excretion (i.e., 64 +/- 8.4 mlU/h). The highly sensitive rat interstitial cell testosterone bioassay for LH also demonstrated a marked decline in LH to undetectable levels in 17/19 subjects. Clinical results with [D-Leu6-des-Gly-NH2(10)]-GnRH-A simulate those achieved by surgical castration in men with prostatic cancer as suggested by available preliminary data.
Adenocarcinoma↗