Effects of Age, Sex, Obesity, and Pregnancy on Plasma Diphenylhydantoin Levels

Sherwin, Allan L.; Loynd, J. S.; Bock, George; Sokolowski, Catherine

doi:10.1111/j.1528-1157.1974.tb04025.x

Cited by 45 publications

(13 citation statements)

References 19 publications

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“…At 8 weeks post partum, phenytoin concentrations had increased, but were still lower than in the early part of pregnancy. In contrast, Sherwin et al (1974) did not find significant changes in the plasma phenytoin concentrations during pregnancy.…”

contrasting

confidence: 69%

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The Pharmacokinetics of Antiarrhythmic Agents in Pregnancy and Lactation

Mitani

Steinberg

Lien

et al. 1987

Clinical Pharmacokinetics

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The pharmacokinetics of various drugs may be profoundly altered during different stages of pregnancy, parturition, and lactation. Gastrointestinal absorption or bioavailability of drugs may vary due to changes in gastric secretion and motility. Various haemodynamic changes such as an increase in cardiac output, blood volume, and renal plasma flow may affect drug disposition and elimination. The increase in blood volume and total body water which occurs during pregnancy can alter the volume of distribution for various drugs. Although exact quantifications are not easy, these changes in pharmacokinetic parameters should be considered when dosing antiarrhythmic agents in pregnant women. Plasma protein concentrations and drug binding capacity are altered in the mother and fetus as pregnancy advances. With highly protein bound drugs, these changes may be clinically significant, as the pharmacological efficacy and toxicity are presumed to be related to the concentration of free drug in both the mother and fetus. In some instances, the fetus may be susceptible to greater drug toxicity as free drug concentrations may be underestimated by measurement of total drug concentrations. Changes in maternal drug metabolism and metabolism by the fetoplacental unit also contribute to alterations in the pharmacokinetics of drugs. As the placenta contains many metabolising enzymes, biotransformation of drugs at this site could potentially convert a drug into an active metabolite, or prevent fetal exposure to a toxic drug. Placental transfer of drugs, leading to toxicity in the fetus, is a major concern in the pharmacological management of the pregnant patient. The passage of individual drugs will vary depending on their apparent volumes of distribution, degree of protein binding the rates of metabolic conversion and excretion within the placenta and fetus, the pH difference between the maternal and fetal fluids, and maternal haemodynamic changes. Drug properties such as lipid solubility, protein binding characteristics, and ionisation constant (pKa) also influence the placental passage of drugs. For weakly basic antiarrhythmic agents, the fetal drug concentration may potentially exceed the maternal plasma concentration when the fetal pH is lowered as in the case of fetal acidosis; this is due to 'ion trapping'. Additionally, higher free drug concentrations of these basic drugs may exist, due to decreased alpha 1-acid glycoprotein concentration and binding affinity in the fetus. Lignocaine (lidocaine) has been shown to enter fetal plasma rapidly with fetal-maternal concentration ratios in the range of 0.52 to 0.66.(ABSTRACT TRUNCATED AT 400 WORDS)

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contrasting

confidence: 69%

“…Phenytoin appears to readily cross the placenta, with some individual variation, but 65 to 100% of the maternal plasma concentrations were found in the fetal cord plasma (Landon & Kirkley 1979;Rane et al 1974;Sherwin et al 1974). The drug has also been detected in amniotic fluid, but concentrations were lower than in the cord plasma.…”

mentioning

confidence: 90%

The Pharmacokinetics of Antiarrhythmic Agents in Pregnancy and Lactation

Mitani

Steinberg

Lien

et al. 1987

Clinical Pharmacokinetics

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“…In contrast, other studies have failed to find a significant age effect on PHT pharmacokinetics. 10,[21][22][23][24] The conflicting reports regarding an age effect on PHT pharmacokinetics may be due to several reasons. 5 Most other investigations assumed that plasma concentrations were measured under steady-state conditions and PHT bioavailability was similar across age groups.…”

Section: Figure 2 Distribution Of Phenytoin Half-lives In Women (Closmentioning

confidence: 93%

Phenytoin half-life and clearance during maintenance therapy in adults and elderly patients with epilepsy

Ahn¹,

Cloyd²,

Brundage³

et al. 2008

Neurology

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“…V max was also found to be significantly higher in Japanese who were taking phenytoin and other anticonvulsants (AEDs and benzodiazepines) as compared with taking phenytoin only. 21,22 Additionally, the liver weight of children, which increases with age, has also been found to correlate with BSA but not body weight. For patients' demographics, only BSA was found to have a significant effect on the value of V max in this study.…”

Section: Discussionmentioning

confidence: 99%