Bioequivalence and Bioavailability Forum

Dear Mahesh

Just one point to clarify

❝ Dose: single ring for 21 days( Per day ring release 0.015 mg EE and 0.12 mg Etonogestrel) “that mean is like a multiple dose study“ ?

Nope, it does not mean like multiple dose study, it would be like controlled release formulation releasing drug as a zero order release at the rate of 0.015 mg/24 hr and/or 0.12 mg/24 hr. (You can assume it similar to that of any long acting IM injections)

❝ Draft guidance mentioned:

❝ Two way cross over

❝ Bioequivalence based on (90% CI): Ethinyl estradiol and etonogestrel

❝ What is the primary PK parameters ? is it Cmax, AUC0-t and AUC0-∞ or Css (Steady state parameters) ?

❝ What’s the sampling schedule for this study ?

For study related details look for following papers

1. PHARMCOKINETICS OF 3-KETO-DESCZESTREL AND ETHINYLESTRADIOL RELEASED FROH DIFFERENT TYPES OF CONTRACEP VANGINAL RINGS C.J. Timmer, D.Apter and G. Voortman, Contraception DECEMBER 1990 VOL. 4 NO. 6
   
2. Comparison of ethinyl estradiol pharmacokinetics in three hormonal contraceptive formulations: the vaginal ring, the transdermal patch and an oral contraceptive, Contraception 72 (2005) 168–174
   
3. Pharmacokinetics of Etonogestrel and Ethinylestradiol Released from a Combined Contraceptive Vaginal Ring. Clinical Pharmacokinetic 2000 Sep; 39 (3): 233-242
   
4. Absence of Pharmacokinetic Interactions of the Combined Contraceptive Vaginal Ring NuvaRing with Oral Amoxicillin or Doxycycline in Two Randomised Trials; Clin Pharmacokinet 2005; 44 (4)

Also check Drugs@Fda look for page 17 onwards.

Hope this would be of some use.