Target‐Mediated Drug Disposition (TMDD) Modeling of an Anti‐TFPI Antibody (MG1113) in Cynomolgus Monkeys to Predict Human Pharmacokinetics and Pharmacodynamics

2021 ◽  
Author(s):  
Eun‐young Kwak ◽  
Min ju Kim ◽  
Jin hyun Park ◽  
Ha wook Jung ◽  
Myung Eun Jung
Keyword(s):  
Drug Disposition ◽  
Human Pharmacokinetics ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Cynomolgus Monkeys ◽  
Target Mediated Drug Disposition

scholarly journals Target-mediated drug disposition and prolonged liver accumulation of a novel humanized anti-CD81 monoclonal antibody in cynomolgus monkeys

mAbs ◽  
2013 ◽  
Vol 5 (5) ◽  
pp. 776-786 ◽  
Author(s):  
Vladimir Vexler ◽  
Li Yu ◽  
Chandrasena Pamulapati ◽  
Rosario Garrido ◽  
Hans Peter Grimm ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Drug Disposition ◽  
Cynomolgus Monkeys ◽  
Target Mediated Drug Disposition

Pharmacokinetics and pharmacodynamics of testosterone enanthate and dihydrotestosterone enanthate in non-human primates

1990 ◽  
Vol 122 (4) ◽  
pp. 432-442 ◽  
Author(s):  
Gerhard F. Weinbauer ◽  
Bettina Jackwerth ◽  
Yong-Dal Yoon ◽  
Hermann M. Behre ◽  
Ching-Hei Yeung ◽  
...  
Keyword(s):  
Gnrh Agonist ◽  
Half Life ◽  
Rhesus Monkeys ◽  
Serum Testosterone ◽  
Testosterone Enanthate ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Elimination Phase ◽  
Cynomolgus Monkeys ◽  
Ejaculate Size ◽  
Testicular Size

Abstract. The pharmacokinetics and pharmacodynamics of testosterone enanthate and dihydrotestosteroneenanthate were compared in orchidectomized cynomolgus monkeys (Macaca fascicularis) and in intact GnRH agonist-suppressed rhesus monkeys (Macaca mulatta). Following a single im injection of 32.8 mg testosterone enanthate or 32.7 mg dihydrotestosteroneenanthate, i.e. 23.6 mg of pure steroid, in the orchidectomized cynomolgus monkeys, serum testosterone and dihydrotestosterone levels rose to 400 and 800% of baseline, respectively, within 24 h. Androgen levels remained in that range for 3-5 days followed by a continuous decline until baseline values were attained after 4-5 weeks. The areas under the testosterone- and dihydrotestosterone-curves did not differ significantly 2290±340 (dihydrotestosterone-enanthate) vs 2920±485 (testosteroneenanthate) suggesting that similar amounts of steroid had been released from the respective ester preparation. Mean half-life estimates of the terminal elimination phase were 4 and 7 days for testosterone-enanthate and dihydrotestosterone-enanthate, respectively. In a second experiment rhesus monkeys received, at 4-weekly intervals, sc implantation of a biodegradable polylactic:polyglycolide rod loaded with the GnRH agonist buserelin. The last injection was given during week 20. GnRH agonist treatment suppressed serum bioactive LH, testosterone and dihydrotestosterone levels, testicular size, sperm production, and seminal carnitine content. The ejaculatory response to electrostimulation and the masturbatory behaviour were abolished. Testosterone or dihydrotestosterone injections at the same doses as above were given in week 10, 14, 17 and 20 of GnRH agonist treatment. Serum testosterone and dihydrotestosterone levels were stimulated 9- and 4-fold, respectively. Mean half-life estimates for testosterone-enanthate and dihydrotestosterone were 5 and 7 days, respectively. Both ester preparations completely restored the ejaculatory response, ejaculate size, masturbatory behaviour, and seminal carnitine levels. In conclusion, androgen substitution with dihydrotestosterone-enanthate, in equivalent doses, is as effective as testosterone-enanthate in restoring reproductive functions in hypogonadal monkeys.

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