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International Journal of Clinical Pharmacy

, Volume 40, Issue 5, pp 1010–1018 | Cite as

Population pharmacokinetics of theophylline in adult Chinese patients with asthma and chronic obstructive pulmonary disease

  • Yanjiao Ma
  • Ling Xue
  • Xin Chen
  • Yingbo Kang
  • Yong WangEmail author
  • Liqing WangEmail author
Research Article

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.

Keywords

Asthma China CYP1A2 genotypes Population pharmacokinetics Theophylline 

Notes

Acknowledgements

The authors thank the physicians for their work and the patients for their participation.

Funding

This research was supported by the National Natural Science Foundation for Young Scientists of China (No. 81302846).

Conflicts of interest

The authors declare no conflicts of interest.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PharmacyZhujiang Hospital of Southern Medical UniversityGuangzhouChina
  2. 2.Department of Clinical PharmacologyThe First Affiliated Hospital of Soochow UniversitySuzhouChina
  3. 3.Department of RespirationZhujiang Hospital of Southern Medical UniversityGuangzhouChina
  4. 4.Department of PharmacyThe First Affiliated Hospital of Shantou University Medical CollegeShantouChina
  5. 5.Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhouChina

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