July 23, 2016
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Aygestin

"Investigators from the Women's Health Initiative (WHI) Hormone Trials are reaffirming conclusions that hormone therapy is not recommended for the prevention of chronic disease, but may remain a reasonable option for the short-term management "...

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Aygestin




CLINICAL PHARMACOLOGY

Norethindrone acetate induces secretory changes in an estrogen-primed endometrium. On a weight basis, it is twice as potent as norethindrone.

Pharmacokinetics

Absorption

Norethindrone acetate is completely and rapidly deacetylated to norethindrone (NET) after oral administration, and the disposition of norethindrone acetate is indistinguishable from that of orally administered norethindrone. Norethindrone acetate is rapidly absorbed from AYGESTIN tablets, with maximum plasma concentration of norethindrone generally occurring at about 2 hours post-dose. The pharmacokinetic parameters of norethindrone following single oral administration of AYGESTIN in 29 healthy female volunteers are summarized in Table 1.

Table 1: Pharmacokinetic Parameters after a Single Dose of AYGESTIN® in Healthy Women

  AYGESTIN®
(n = 29)
Arithmetic Mean ± SD
Norethindrone (NET)
AUC (0-inf)(ng/ml*h) 166.90 ± 56.28
Cmax (ng/ml) 26.19 ± 6.19
tmax (h) 1.83 ± 0.58
t½ (h) 8.51 ± 2.19
AUC = area under the curve,
Cmax = maximum plasma concentration,
tmax = time at maximum plasma concentration,
t½ = half-life,
SD = standard deviation

Figure 1: Mean Plasma Concentration Profile after a Single Dose of 5 mg Administered to 29 Healthy Female Volunteers under Fasting Conditions

Mean Plasma Concentration Profile - Illustration

Effect Of Food

The effect of food administration on the pharmacokinetics of AYGESTIN has not been studied.

Distribution

Norethindrone is 36% bound to sex hormone-binding globulin (SHBG) and 61% bound to albumin. Volume of distribution of norethindrone is about 4 L/kg.

Metabolism

Norethindrone undergoes extensive biotransformation, primarily via reduction, followed by sulfate and glucuronide conjugation. The majority of metabolites in the circulation are sulfates, with glucuronides accounting for most of the urinary metabolites.

Excretion

Plasma clearance value for norethindrone is approximately 0.4 L/hr/kg. Norethindrone is excreted in both urine and feces, primarily as metabolites. The mean terminal elimination half-life of norethindrone following a single dose administration of AYGESTIN is approximately 9 hours.

Special Populations

Geriatrics

The effect of age on the pharmacokinetics of norethindrone after AYGESTIN administration has not been evaluated.

Race

The effect of race on the disposition of norethindrone after AYGESTIN administration has not been evaluated.

Renal Insufficiency

The effect of renal disease on the disposition of norethindrone after AYGESTIN administration has not been evaluated. In premenopausal women with chronic renal failure undergoing peritoneal dialysis who received multiple doses of an oral contraceptive containing ethinyl estradiol and norethindrone, plasma norethindrone concentration was unchanged compared to concentrations in premenopausal women with normal renal function.

Hepatic Insufficiency

The effect of hepatic disease on the disposition of norethindrone after AYGESTIN administration has not been evaluated. However, AYGESTIN is contraindicated in markedly impaired liver function or liver disease.

Drug Interactions

No pharmacokinetic drug interaction studies investigating any drug-drug interactions with AYGESTIN have been conducted.

Last reviewed on RxList: 4/19/2016
This monograph has been modified to include the generic and brand name in many instances.

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