Binding Parameters of Valproic Acid to Serum Protein in Healthy Adults at Steady State

Kodama, Yasuo; Koike, Yuichi; Kimoto, Hiroo; Yasunaga, Fumitaka; Takeyama, Masaharu; Teraoka, Iwao; Fujii, Isao

doi:10.1097/00007691-199202000-00009

Cited by 28 publications

(18 citation statements)

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“…The hospitals involved in this study had TDM laboratories that were certificated by China Ministry of Health. 7,28,29 Secondly, TDM effects 30 may also be responsible. Although only routine trough concentrations were used in this analysis, it allows reliable estimates of CL/F and its influential effects.…”

Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetics of Valproic Acid in Adult Chinese Epileptic Patients and its Application in an Individualized Dosage Regimen

Jiao

Wang

et al. 2015

Therapeutic Drug Monitoring

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Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetics of Valproic Acid in Adult Chinese Epileptic Patients and its Application in an Individualized Dosage Regimen

Jiao

Wang

et al. 2015

Therapeutic Drug Monitoring

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“…7,8 In this study, we determined, using this binding equation, the in vivo population binding parameters of valproic acid to serum proteins between male and female pediatric patients with epilepsy receiving monotherapy. 7,8 In this study, we determined, using this binding equation, the in vivo population binding parameters of valproic acid to serum proteins between male and female pediatric patients with epilepsy receiving monotherapy.…”

confidence: 99%

“…In previous studies, we determined the in vivo population binding parameters of valproic acid to serum proteins after a single and repeated dosing of valproic acid in healthy young adults and defined a binding equation for the relation between total and unbound serum concentrations that was derived from the Scatchard equation. 7,8 In this study, we determined, using this binding equation, the in vivo population binding parameters of valproic acid to serum proteins between male and female pediatric patients with epilepsy receiving monotherapy. The binding parameters of valproic acid to serum proteins were also determined in prepubescent (< 10 years of age) and pubescent (≥ 10 years) groups.…”

confidence: 99%

No Effect of Gender or Age on Binding Characteristics of Valproic Acid to Serum Proteins in Pediatric Patients with Epilepsy

Kodama

Kuranari

et al. 1999

The Journal of Clinical Pharma

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The gender- and age-related binding characteristics of valproic acid to serum proteins were determined in the pediatric population. Serum samples examined in the study were obtained from 61 pediatric patients (28 males, 33 females) with epilepsy on valproic acid monotherapy. Their ages ranged from 1 to 15 years (mean age with [SD]: 7.8 [3.9] years; < 10 years, n = 41; > or = 10 years, n = 20). The in vivo population binding parameters of valproic acid to serum proteins and theoretical minimal unbound serum fraction (fu) of valproic acid were determined in (1) all, (2) male and female subgroups, and (3) prepubescent (< 10 years) and pubescent (> or = 10 years) subgroups. The association constant (K) was approximately 1.4 times higher in male (0.018 L/mumol) than in female (0.013 L/mumol) patients, while the total concentration of binding sites (n(Pt)) was 1.2 times greater in female (1235 mumol/L) than in male (997 mumol/L) patients. The fu was 0.053 and 0.059 for male and female patients, respectively. The value of K was approximately 1.6 times higher in the pubescent (0.019 L/mumol) than in the prepubescent (0.012 L/mumol) patients, while the n(Pt) was 1.2 times higher in the prepubescent (1244 mumol/L) than in the pubescent (1057 mumol/L) patients. The fu was 0.063 for the prepubescent and 0.047 for the pubescent patients. No significant differences were observed in binding characteristics of valproic acid to serum proteins between male and female or younger and older patients. However, the differences in valproic acid binding to serum proteins appear to be relatively larger in binding affinity than in binding capacity between the two groups. Because no significant differences were observed in serum concentrations of total and unbound valproic acid, albumin, or free fatty acids between any subgroups (male and female, younger and older), the results suggest that gender or age may not be factors for the determination of the binding characteristics of valproic acid to serum proteins in pediatric patients.

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“…In vivo studies show that phenytoin has a single population of binding sites on the albumin molecule ( 14). Therefore, the relationship between total and unbound serum phenytoin concentrations can be expressed by using the Scatchard equation, which was also used to examine the relationship between total and unbound serum concentrations of valproic acid ( 15, 16). In the present study, we determined, using this binding equation, the in vivo population binding parameters of phenytoin to serum proteins in Japanese patients with epilepsy receiving monotherapy.…”

Section: Introductionmentioning

confidence: 99%

“…for the determination of valproic acid binding characteristics to plasma proteins ( 22). The association constant ( K ) and total concentration of binding sites ( n ( Pt ) were estimated by iteratively reweighed least squares regression analysis to the binding equation shown below ( 15, 16) derived from the Scatchard equation for a one‐site binding model.…”

Section: Introductionmentioning

confidence: 99%

Serum protein binding kinetics of phenytoin in monotherapy patients

Kodama

Shinozawa

et al. 1998

Journal of Clinical Pharmacy and Therapeutics

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Binding Parameters of Valproic Acid to Serum Protein in Healthy Adults at Steady State

Cited by 28 publications

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Population Pharmacokinetics of Valproic Acid in Adult Chinese Epileptic Patients and its Application in an Individualized Dosage Regimen

Population Pharmacokinetics of Valproic Acid in Adult Chinese Epileptic Patients and its Application in an Individualized Dosage Regimen

No Effect of Gender or Age on Binding Characteristics of Valproic Acid to Serum Proteins in Pediatric Patients with Epilepsy

Serum protein binding kinetics of phenytoin in monotherapy patients

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