Effect of age, height, weight and sex on serum phenytoin concentration in epileptic patients.

Houghton, G. W.; Richens, A.; Leighton, Monica

doi:10.1111/j.1365-2125.1975.tb01583.x

Cited by 73 publications

(31 citation statements)

References 16 publications

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“…When steady-state plasma con centrations of PHT were used as an index of sex-based differences in PHT metabolism, they were found to be 20% lower among women though this difference was not a sta tistically significant one [7], Direct compari sons of our estimates of PHT CLujn, with those of other investigators cannot be made. However, given that CLuinl is the ratio of Vmax/Km where Km is referenced to unbound drug [13], and allowing Km to be set at 0.57 mg/1 (population Km referenced to total PHT concentrations [17] multiplied by a nominal free fraction of 0.1) and Vmax at 0.247 mg/kg/h [17], one can estimate a CLuin[ of 433 ml/h/kg to which our value (all subjects) of 483 (± 178) compares favora bly.…”

Section: Discussioncontrasting

confidence: 49%

Use of Three Probes to Assess the Influence of Sex on Hepatic Drug Metabolism

et al. 1987

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Clearances of phenytoin (PHT), ethosuximide, and theophylline were estimated by a single-dose, single-sample strategy in healthy, young adult men and women. PHT concentrations were measured in salivary ultrafiltrates, ethosuximide concentrations were measured in saliva, and theophylline concentrations were measured in plasma. Estimates of the clearances of these three probes of hepatic drug-metabolizing enzymes revealed a trend toward slightly lower clearances among women compared to men: mean PHT clearance 15 % lower, ethosuximide clearance 27% lower, and theophylline clearance 14% lower. However, only differences in ethosuximide clearances were statistically significant. The use of oral contraceptive steroid (OCS) drugs on PHT and ethosuximide clearance was examined, and no significant effects were detected.

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Section: Discussioncontrasting

confidence: 49%

Use of Three Probes to Assess the Influence of Sex on Hepatic Drug Metabolism

et al. 1987

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“…The large interindividual variation in this parameter is probably due to the wide variation in normal renal function and renal lithium clearance (Schou, 1969). Similarly, small contributions of age to large interindividual variation have been recently demonstrated for plasma antipyrine clearances (Vestal, Norris, Tobin, Cohen, Shock & Andres, 1975) and serum phenytoin concentrations (Houghton, Richens & Leighton, 1975).…”

Section: Discussionmentioning

confidence: 99%

Age as a factor affecting lithium therapy.

Hewick¹,

Newbury²,

Hopwood³

et al. 1977

Brit J Clinical Pharma

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1We examined the case notes of 82 psychiatric out-patients (aged 21-84 years) receiving lithium prophylaxis and with steady-state plasma lithium levels. 2 The mean weight-related daily dose of lithium prescribed decreased by about 50% between the third and eighth decades. 3 The corresponding steady-state plasma lithium levels showed a less marked tendency to decrease, this only being seen in the seventh and eighth decades. 4 In patients aged 50 years or over the daily lithium dose required to give a plasma level of 1 mmol 1-1 (0.50 mmol kg-') was significantly lower than that (0.65 mmol kg-') in patients aged under 50 years (P < 0.005, Student's t-test). In patients aged 70-79 years this dose was 31 % lower than in patients under 50 years. However, interindividual variation was great and it was estimated that age only contributed about 14% to the total interpatient variation. 5Of the 36 patients under 50 years of age, 42% had minor lithium side-effects and 17% were not optimally controlled with lithium. The corresponding figures for the 46 'older' patients were 46% and 28%. 6 Generally the 50% dosage reduction seemed necessary to compensate for an age-related decrease in lithium excretion and to reduce lithium side effects to a level comparable to that acceptable in younger patients.

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“…Genetic and environmental factors can influence considerably the rate of metabolism of the drug, contributing to large interindividual differences in the serum levels associated with a fixed dosage regimen (Houghton, Richens & Leighton, 1975). Variations of steady state levels within individuals receiving the same dose of the drug also occur and are usually explained as the result of non-compliance, differences in bioavailability or interactions with other antiepileptic drugs.…”

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confidence: 99%