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Population pharmacokinetics of primaquine and the effect of hepatic and renal dysfunction: An exploratory approach
Kannan Sridharan1, Chenna Keshava Reddy Sannala2, Surulivelrajan Mallayasamy3, Ayyappa Chaturvedula2, Prashant Kadam1, Nivrutti Hase4, Akash Shukla5, Nithya Gogtay1, Urmila Thatte1
1 Department of Clinical Pharmacology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India
2 GVK Biosciences Private Limited, Hyderabad, Telangana, India
3 Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka, India
4 Department of Nephrology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India
5 Department of Gastroenterology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, India
Correspondence Address:
Dr. Urmila Thatte
Department of Clinical Pharmacology, Seth GS Medical College and KEM Hospital, Parel, Mumbai - 400 012, Maharashtra
India
OBJECTIVES: We attempted to develop a population pharmacokinetic model for primaquine (PQ) and evaluate the effect of renal and hepatic dysfunction on PQ pharmacokinetics.
MATERIALS AND METHODS: The data were collected from a prospective, nonrandomized clinical study in healthy volunteers and patients with mild-moderate hepatic dysfunction and renal dysfunction. Model development was conducted using NONMEM® software, and parameter estimation was conducted using first-order conditional estimation with interaction method.
RESULTS: Final data included a total of 53 study participants (13 healthy individuals, 12 with mild hepatic dysfunction, 6 with moderate hepatic dysfunction, and 22 with renal dysfunction) with 458 concentrations records. Absorption rate constant (Ka) was constrained to be higher than elimination rate constant to avoid flip-flop situation. Mild hepatic dysfunction was a significant covariate on volume of distribution, and it is approximately three folds higher compared to other subjects. Fixed effects parameter estimates of the final model – absorption rate constant (Ka), volume of distribution (V), and clearance (CL) – were 0.95/h, 498 L, and 39 L/h, respectively. Between-subject variability estimates (% CV) on Ka, V, and CL were 77, 66, and 65, respectively. Residual error was modeled as combination error model with the parameter estimates for proportion error 12% CV and additive error (standard deviation) 1.5 ng/ml.
CONCLUSION: Population pharmacokinetic modeling showed that the volume of distribution of PQ in subjects with moderate hepatic dysfunction increases approximately three folds resulting in a significantly lower plasma concentration.
How to cite this article:
Sridharan K, Reddy Sannala CK, Mallayasamy S, Chaturvedula A, Kadam P, Hase N, Shukla A, Gogtay N, Thatte U. Population pharmacokinetics of primaquine and the effect of hepatic and renal dysfunction: An exploratory approach.Indian J Pharmacol 2019;51:17-24
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How to cite this URL:
Sridharan K, Reddy Sannala CK, Mallayasamy S, Chaturvedula A, Kadam P, Hase N, Shukla A, Gogtay N, Thatte U. Population pharmacokinetics of primaquine and the effect of hepatic and renal dysfunction: An exploratory approach. Indian J Pharmacol [serial online] 2019 [cited 2023 Sep 28 ];51:17-24
Available from: https://www.ijp-online.com/article.asp?issn=0253-7613;year=2019;volume=51;issue=1;spage=17;epage=24;aulast=Sridharan;type=0 |
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