Pharmacokinetics of single-dose primaquine in patients with chronic kidney dysfunction

Kulkarni, Shrirang Vasant; Shah, Sanjana R; Kadam, Prashant P; Sridharan, Kannan; Hase, N K; Shetty, Partha; Thatte, Urmila M; Gogtay, Nithya J

doi:10.4103/0253-7613.114997

Cited by 2 publications

(1 citation statement)

References 20 publications

(26 reference statements)

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“…CL and volume of distribution were found to be in agreement to the traditional pharmacokinetic studies from various other populations[516] including the previous one from the same center. [17]…”

Section: Discussionmentioning

confidence: 99%

Population pharmacokinetics of primaquine and the effect of hepatic and renal dysfunction: An exploratory approach

Sridharan

Sannala

Mallayasamy³

et al. 2019

Indian J Pharmacol

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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.

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Section: Discussionmentioning

confidence: 99%

Population pharmacokinetics of primaquine and the effect of hepatic and renal dysfunction: An exploratory approach

Sridharan

Sannala

Mallayasamy³

et al. 2019

Indian J Pharmacol

Self Cite

View full text Add to dashboard Cite

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Drug interactions with antimalarial medications in older travelers: a clinical guide

Lewis

Gregorian

Portillo

et al. 2019

Journal of Travel Medicine

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Increasingly older adults are traveling to international destinations with malaria as a present risk. Surveillance systems indicate that older adults are more likely to suffer severe complications from malaria. The role of health care providers in selecting an appropriate medication for chemoprophylaxis or treatment of malaria in adults becomes more difficult as older adults undergo physiologic changes that alter the pharmacokinetic and pharmacodynamic nature of medications potentially causing increased drug interactions, adverse events and altered drug action. A comprehensive literature search from 1970 to present, with a focus on the past 10 years, was conducted on drug interactions, pharmacokinetic and pharmacodynamic effects on antimalarials in adults. It was determined that due to pharmacodynamic and pharmacokinetic changes in older adults, especially renal and cardiovascular, special attention should be given to this population of travelers in order to minimize the likelihood of adverse events or altered drug efficacy. Antimalarial drug–disease interactions in older adults can occur more often due to QT prolongation, exacerbation of hypoglycemia, decreased renal elimination and decreased hepatic metabolism. Older antimalarials have well-documented drug–drug interactions. Tafenoquine, a new antimalarial, requires glucose-6-phosphate dehydrogenase screening like primaquine and monitoring of new potential drug interaction with MATE1 and OCT2 substrates. While drug–drug interactions in older travelers may occur more often as a result of polypharmacy, data did not indicate adverse reactions or decreased drug efficacy is greater compared with younger adults. Overall, with the exception of recently approved tafenoquine, much is known about antimalarial drug and disease interactions, but new drugs are always being approved, requiring travel health providers to understand the pharmacokinetics and pharmacodynamics of antimalarial drugs to predict the impact on safety and efficacy in travelers. This guide provides travel health providers with valuable insights on potential outcomes associated with drug interactions in adults and recommended monitoring or drug regimen modification.

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Pharmacokinetics of single-dose primaquine in patients with chronic kidney dysfunction

Cited by 2 publications

References 20 publications

Population pharmacokinetics of primaquine and the effect of hepatic and renal dysfunction: An exploratory approach

Population pharmacokinetics of primaquine and the effect of hepatic and renal dysfunction: An exploratory approach

Drug interactions with antimalarial medications in older travelers: a clinical guide

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