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Population pharmacokinetics of theophylline in adult Chinese patients with asthma and chronic obstructive pulmonary disease.
Ma, Yanjiao; Xue, Ling; Chen, Xin; Kang, Yingbo; Wang, Yong; Wang, Liqing.
Afiliação
  • Ma Y; Department of Pharmacy, Zhujiang Hospital of Southern Medical University, Guangzhou, 510282, Guangdong, China.
  • Xue L; Department of Clinical Pharmacology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu, China.
  • Chen X; Department of Respiration, Zhujiang Hospital of Southern Medical University, Guangzhou, 510282, Guangdong, China.
  • Kang Y; Department of Pharmacy, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, Guangdong, China.
  • Wang Y; Department of Pharmacy, Zhujiang Hospital of Southern Medical University, Guangzhou, 510282, Guangdong, China. 18819132903@163.com.
  • Wang L; Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, Guangdong, China. 18819132903@163.com.
Int J Clin Pharm ; 40(5): 1010-1018, 2018 Oct.
Article em En | MEDLINE | ID: mdl-29777329
ABSTRACT
Background Theophylline has a narrow therapeutic range and large interindividual variability in blood levels, so a thorough understanding of its pharmacokinetic characteristics is essential. Population pharmacokinetic (PPK) approaches could achieve it and many PPK studies of theophylline have been reported in infants. However, none was conducted in Chinese adults and none has explored the effect of CYP1A2 genotypes on the PPK characteristics of theophylline in adults. Objective To evaluate the PPK characteristics of theophylline and to assess the possible influence of covariates, including CYP1A2 genotypes, on theophylline clearance in Chinese adult patients. Setting The study is conducted at the department of respiration in Zhujiang Hospital, Guangzhou, China. Methods Theophylline concentrations were obtained from eligible patients and were measured by high performance liquid chromatography. The polymorphisms of - 3860G > A, - 163C > A, C5347T (CYP1A2*1B) and G-3113A were genotyped using a direct sequencing method. Then, CYP1A2 genotypes, age, fat-free mass (FFM) and other covariates were used to develop a PPK model by NONMEM software. Bootstrap analysis was used to asses the accuracy and prediction of the PPK model. Main outcome measure The concentration and clearance of theophylline. Results A total of 134 theophylline concentrations from 95 patients were obtained. The final model was as follows CL/F(L/h) = 4.530 × (FFM/56.1)0.75 × 0.713CYP1A2*1B, the inter-individual variability in clearance/bioavailability (CL/F) was 44.0%, and the residual variability was 9.8%. The final model was proved to be reliable by bootstrap analysis. Conclusion Theophylline clearance was significantly associated with FFM and CYP1A2*1B genotypes in Chinese adult patients.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Asma / Teofilina / Broncodilatadores / Citocromo P-450 CYP1A2 / Doença Pulmonar Obstrutiva Crônica / Povo Asiático Tipo de estudo: Prognostic_studies / Screening_studies Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Int J Clin Pharm Ano de publicação: 2018 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Asma / Teofilina / Broncodilatadores / Citocromo P-450 CYP1A2 / Doença Pulmonar Obstrutiva Crônica / Povo Asiático Tipo de estudo: Prognostic_studies / Screening_studies Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Int J Clin Pharm Ano de publicação: 2018 Tipo de documento: Article País de afiliação: China