Concentration of ibuprofen in cervical mucus

Salas-Herrera, I. G.; Pearson, Richard M.; Turner, Paul

doi:10.1111/j.2042-7158.1991.tb06653.x

Cited by 3 publications

(1 citation statement)

References 12 publications

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“…Data (n = 389) were taken from three publications reporting an estimate of individual clearance estimates in premature neonates, three reporting population clearance estimates in infants, 11 in children 2‐15 years (1 with individual Bayesian estimates available, and 9 with population clearances) and 13 adult studies (1 with individual Bayesian estimates available and 12 with population clearance estimates).…”

Section: Resultsmentioning

confidence: 99%

A target concentration strategy to determine ibuprofen dosing in children

Anderson

Hannam

2019

Pediatric Anesthesia

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Background Ibuprofen is widely used for ductus arteriosus closure in premature neonates and for analgesia in children and adults. There are no maturation descriptors of clearance. This lack of maturation understanding limits dosing recommendations from premature neonates to adulthood. Methods Published clearance estimates from different aged patients determined after administration from time‐concentration profiles were used to construct a maturation model based on size and age. Curve fitting was performed using nonlinear mixed‐effects models. A target concentration strategy was used to estimate maintenance dose at different ages. Results There were three publications reporting an estimate of individual clearance estimates in premature neonates, three reporting population clearances in infants, 11 in children 2‐15 years (1 with individual and 9 with population clearances), and 13 adult studies (1 with individual and 12 with population clearances). Clearance maturation, standardized to a 70 kg person was described using the Hill equation. Mature clearance was 3.81 (CV 15.5%, 95%CI 3.72, 3.92) L/h/70 kg. The maturation half‐time was 36.8 (CV 9.2%, 95%CI 34.7, 40.9) weeks postmenstrual age and the Hill coefficient 11.5 (95%CI 8.1, 15). A target effect of four units (visual analogue scale 0‐10) correlated with an effect site concentration of 6.3 mg/L: a concentration achieved at trough after 400 mg 8 hourly in adults. Conclusion Previously published pharmacokinetic parameters can be used to develop maturation models that address gaps in current knowledge regarding the influence of age on a drug's disposition. Maturation of ibuprofen clearance was rapid and was 90% of adult values by the first month of life in term neonates (ie, 44 weeks postmenstrual age) and 98% of standardized adult estimates by 3 months of age (53 weeks postmenstrual age). Clearance informed dosing predictions in all ages (premature neonate to adult) and matched those doses in common use in children older than 3 months.

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Section: Resultsmentioning

confidence: 99%

A target concentration strategy to determine ibuprofen dosing in children

Anderson

Hannam

2019

Pediatric Anesthesia

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Secretion of drugs into the human female genital tract

Salas-Herrera

Turner

Pearson

1991

Postgraduate Medical Journal

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Drug disposition out of and into the female genital tract has received relatively little attention from clinical pharmacologists. This is surprising, for, at least in about 50% of the population, the vaginal route is available for parenteral drug administration. The systemic bioavailability of drugs after vaginal administration is much greater than after oral administration, not unexpectedly because the venous drainage of the vascular vaginal wall is directly into the inferior vena cava, so by-passing the hepatic circulation.'Propranolol has been successfully administered by the vaginal route in a patient unable to take it orally,2 and, recently, vaginal bromocriptine has been used successfully to treat a prolactinproducing pituitary tumour in a patient in whom side effects precluded oral administration of the drug.3 Subsequent studies in volunteers by the authors of this latter report showed that circulating levels of bromocriptine were significantly higher following vaginal than oral administration.The extent of secretion of drugs into the female genital tract after oral administration is important for several reasons. Firstly, a drug may exert its therapeutic action through its concentration in cervical mucus. For example metronidazole given orally can be used to treat vaginal trichomonas infections.4 Secondly, a drug may exert unwanted effects by reducing sperm motility and fertility.5 Orally administered propranolol has been shown to be highly concentrated in cervical mucus6 and other experiments have shown it to reduce sperm motility in vitro,7 although only at concentrations much higher than those achieved in cervical mucus after therapeutic oral doses. A preliminary study involving insertion of 80 mg propranolol tablets in the vaginas of 198 female volunteers has shown that propranolol is an effective vaginal contraceptive.8The extent to which a drug and its metabolites appear in human body fluids depends on their physicochemical properties, including lipid solubility, protein binding and dissociation constant. Some local factors may also influence their concentration in cervical mucus, including environmental pH and the concentrations of various proteins in the mucus. Albumin and alpha-1-acid glycoprotein (AGP) in serum play an important role in the binding of drugs, but their role in cervical mucus is obscure. The albumin concentration in cervical mucus is merely 1% of that in serum, and AGP is present only in traces during the mid-cycle period when it has been measured.9"10The protein-binding of propranolol and ibuprofen in cervical mucus has been found to be 26% and 66% respectively, and this has not correlated with the concentrations ofeither albumin or AGP.""2 It is unlikely, therefore, that cervical mucus protein concentration is an important determinant of drug disposition into cervical mucus.In order to determine the influence of the physicochemical properties of a drug, namely its lipid solubility, serum protein binding, and dissociation constant (pKa) on its cervical mucus concentration, we ha...

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Clinical Pharmacokinetics of Ibuprofen

Davies

1998

Clinical Pharmacokinetics

396

348

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Ibuprofen is a chiral nonsteroidal anti-inflammatory drug (NSAID) of the 2 arylpropionic acid (2-APA) class. A common structural feature of 2-APANSAIDs is a sp3-hybridised tetrahedral chiral carbon atom within the propionic acid side chain moiety with the S-(+)-enantiomer possessing most of the beneficial anti-inflammatory activity. Ibuprofen demonstrates marked stereoselectivity in its pharmacokinetics. Substantial unidirectional inversion of the R-(-) to the S-(+) enantiomer occurs and thus, data generated using nonstereospecific assays may not be extrapolated to explain the disposition of the individual enantiomers. The absorption of ibuprofen is rapid and complete when given orally. The area under the plasma concentration-time curve (AUC) of ibuprofen is dose-dependent. Ibuprofen binds extensively, in a concentration-dependent manner, to plasma albumin. At doses greater than 600mg there is an increase in the unbound fraction of the drug, leading to an increased clearance of ibuprofen and a reduced AUC of the total drug. Substantial concentrations of ibuprofen are attained in synovial fluid, which is a proposed site of action for nonsteroidal anti-inflammatory drugs. Ibuprofen is eliminated following biotransformation to glucuronide conjugate metabolites that are excreted in urine, with little of the drug being eliminated unchanged. The excretion of conjugates may be tied to renal function and the accumulation of conjugates occurs in end-stage renal disease. Hepatic disease and cystic fibrosis can alter the disposition kinetics of ibuprofen. Ibuprofen is not excreted in substantial concentrations into breast milk. Significant drug interactions have been demonstrated for aspirin (acetylsalicylic acid), cholestyramine and methotrexate. A relationship between ibuprofen plasma concentrations and analgesic and antipyretic effects has been elucidated.

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Concentration of ibuprofen in cervical mucus

Cited by 3 publications

References 12 publications

A target concentration strategy to determine ibuprofen dosing in children

A target concentration strategy to determine ibuprofen dosing in children

Secretion of drugs into the human female genital tract

Clinical Pharmacokinetics of Ibuprofen

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