Route of administration and formulation dependent pharmacokinetics of 17-hydroxyprogesterone caproate in rats

Shaik, Imam H.; Bastian, Jaime; Zhao, Yang; Caritis, Steve N.; Venkataramanan, Raman

doi:10.3109/00498254.2015.1057547

Cited by 9 publications

(5 citation statements)

References 13 publications

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“… 15 In a study of a cremophor:ethanol-based formulation in rats, the half-life was 10.6 hours when given intravenously but was not reached after 120 hours when given intramuscularly. 16 …”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Hydroxyprogesterone Caproate and its Primary Metabolites during Pregnancy

Boggess

Baker²,

Murtha

et al. 2018

AJP Rep

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Objective To measure pharmacokinetics of hydroxyprogesterone caproate (OHPC) and its major metabolites throughout pregnancy. Study Design Thirty women were prescribed OHPC for recurrent preterm birth prevention. Three cohorts of subjects had blood drawn for 7 consecutive days at one of three times: cohort 1 ( n = 6) after the first dose (weeks 16–20), cohort 2 ( n = 8) between weeks 24 and 28, and cohort 3 ( n = 16) between weeks 32 and 36. We measured serum trough levels after week 1 in cohort 1 or after two consecutive weekly doses in cohorts 2 and 3. In 10 subjects, we estimated OHPC terminal half-life at 28 days after their last dose. Results In cohorts 1, 2, and 3, the areas under curve (ng × h/mL) for OHPC were 571.4 ± 195.2, 1,269.6 ± 285.0, and 1,268.0 ± 511.6, respectively. Maximum OHPC levels (ng/mL) were 5.0 ± 1.5, 12.5 ± 3.9, and 12.3 ± 4.9, respectively. The areas under the curve for mono-hydroxylated metabolites were 208.5 ± 92.4, 157.1 ± 64.6, and 211.2 ± 113.1, and maximum concentrations were 1.9 ± 0.7, 1.5 ± 0.7, and 1.8 ± 1.0, respectively. Di-hydroxylated metabolite levels were significantly lower than mono-hydroxylated metabolites. Estimated terminal half-life of OHPC was 16.3 ± 3.6 days and 19.7 ± 6.2 days for the mono-hydroxylated metabolites. Conclusion After the first injection, OHPC maximum serum level was approximately half steady-state level. Measurable metabolites of unknown activity were detected.

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“… 15 In a study of a cremophor:ethanol-based formulation in rats, the half-life was 10.6 hours when given intravenously but was not reached after 120 hours when given intramuscularly. 16 …”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Hydroxyprogesterone Caproate and its Primary Metabolites during Pregnancy

Boggess

Baker²,

Murtha

et al. 2018

AJP Rep

View full text Add to dashboard Cite

show abstract

“…Experimental animals were administered vehicle alone or 17-OHPC subcutaneously at the time of intranasal infection. 17-OHPC was administered at a dose of 2 mg/dam, which previously demonstrated efficacy in preventing adverse neurological outcomes in a mouse model of intrauterine inflammation ( 41 ) and was administered as a single injection due to the prolonged half-life of 17-OHPC when delivered in an oil-based solution [>7 days ( 42 )].…”

Section: Methodsmentioning

confidence: 99%

Suppression of progesterone by influenza A virus mediates adverse maternal and fetal outcomes in mice

Creisher,

Parish,

Lei

et al. 2024

mBio

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Influenza A virus infection during pregnancy can cause adverse maternal and fetal outcomes but the mechanism responsible remains elusive. Infection of outbred mice with 2009 H1N1 at embryonic day (E) 10 resulted in significant maternal morbidity, placental tissue damage and inflammation, fetal growth restriction, and developmental delays that lasted through weaning. Restriction of pulmonary virus replication was not inhibited during pregnancy, but infected dams had suppressed circulating and placental progesterone (P4) concentrations that were caused by H1N1-induced upregulation of pulmonary cyclooxygenase (COX)-1-, but not COX-2-, dependent synthesis and secretion of prostaglandin (PG) F2α. Treatment with 17-α-hydroxyprogesterone caproate (17-OHPC), a synthetic progestin that is safe to use in pregnancy, ameliorated the adverse maternal and fetal outcomes from H1N1 infection and prevented placental cell death and inflammation. These findings highlight the therapeutic potential of progestin treatments for influenza during pregnancy. IMPORTANCE Pregnant individuals are at risk of severe outcomes from both seasonal and pandemic influenza A viruses. Influenza infection during pregnancy is associated with adverse fetal outcomes at birth and adverse consequences for offspring into adulthood. When outbred dams, with semi-allogenic fetuses, were infected with 2009 H1N1, in addition to pulmonary virus replication, lung damage, and inflammation, the placenta showed evidence of transient cell death and inflammation that was mediated by increased activity along the arachidonic acid pathway leading to suppression of circulating progesterone. Placental damage and suppressed progesterone were associated with detrimental effects on perinatal growth and developmental delays in offspring. Treatment of H1N1-infected pregnant mice with 17-OHPC, a synthetic progestin treatment that is safe to use in pregnancy, prevented placental damage and inflammation and adverse fetal outcomes. This novel therapeutic option for the treatment of influenza during pregnancy should be explored clinically.

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“…Experimental animals were administered vehicle alone or 17-OHPC subcutaneously at the time of intranasal infection. 17-OHPC was administered at a dose of 2 mg/dam, which previously demonstrated efficacy in Creisher et al preventing adverse neurological outcomes in a mouse model of intrauterine inflammation (Novak et al, 2018), and was administered as a single injection due to the prolonged half-life of 17-OHPC when delivered in an oil-based solution [>7 days (Shaik et al, 2016)].…”

Section: α-Hydroxyprogesterone Caproate Treatmentmentioning

confidence: 99%

Suppression of progesterone by influenza A virus mediates adverse maternal and fetal outcomes in mice

Creisher,

Parish,

Lei

et al. 2023

Preprint

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Influenza A virus infection during pregnancy can cause adverse maternal and fetal outcomes, but the mechanism responsible remains elusive. Infection of outbred mice with 2009 H1N1 at embryonic day (E) 10 resulted in significant maternal morbidity, placental tissue damage and inflammation, fetal growth restriction, and developmental delays that lasted through weaning. Restriction of pulmonary virus replication was not inhibited during pregnancy, but infected dams had suppressed circulating and placental progesterone (P4) concentrations that were caused by H1N1-induced upregulation of pulmonary cyclooxygenase (COX)-1, but not COX-2-, dependent synthesis and secretion of prostaglandin (PG) F2α. Treatment with 17-α-hydroxyprogesterone caproate (17-OHPC), a synthetic progestin that is safe to use in pregnancy, ameliorated the adverse maternal and fetal outcomes from H1N1 infection and prevented placental cell death and inflammation. These findings highlight the therapeutic potential of progestin treatments for influenza during pregnancy.

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Route of administration and formulation dependent pharmacokinetics of 17-hydroxyprogesterone caproate in rats

Cited by 9 publications

References 13 publications

Pharmacokinetics of Hydroxyprogesterone Caproate and its Primary Metabolites during Pregnancy

Pharmacokinetics of Hydroxyprogesterone Caproate and its Primary Metabolites during Pregnancy

Suppression of progesterone by influenza A virus mediates adverse maternal and fetal outcomes in mice

Suppression of progesterone by influenza A virus mediates adverse maternal and fetal outcomes in mice

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