107 Journal of the association of physicians of india • vol 62 • published on 1st of every month 1st august, 2014 Pharmacokinetics of a Single Dose (15 mg) Primaquine in Chronic Kidney Disease Patients Undergoing Haemodialysis Kannan Sridharan1, Prashant P Kadam1, Nithya J Gogtay1, Nivrutti K Hase2, Urmila M Thatte 1 The study was carried out between June 2010 and August 2011 after obtaining approval from the institutional review board (IRB) – committee for academic research ethics (CARE), Seth GS medical college and KEM hospital, Mumbai, India. Written informed consent was obtained from participants, those with CKD [stage V (on dialysis)] as per national kidney foundation – kidney disease outcome q u a l i t y i n i t i a t i ve ( N K F - K D O Q I ) , 5 a normal G6PD activity and hemoglobin greater than 7 g/dl were recruited. None were receiving concomitant medications known to interact with primaquine. Sir, P rimaquine, an 8-aminoquinoline, approved in 1952, is used as an anti relapse agent for P. vivax (15 mg/d x 14) and gametocidal for P. falciparum (45 mg single dose). Although the drug is widely used, there is a dearth of information regarding its disposition in patients with chronic kidney disease (CKD). The drug preferentially binds to the acute phase reactant protein alpha 1-acid glycoprotein (AAG), 1 which is elevated in patients with uraemia as well as during haemodialysis. 2 Furthermore, the incidence of malaria associated acute renal failure (MARF) is increasing and haemodialysis was shown to be effective. 3,4 We present in this letter, data on two patients where pharmacokinetics of primaquine was evaluated in patients with CKD undergoing haemodialysis. After an oral single dose of 15 mg Primaquine following 30 minutes after a standardised breakfast, 5 ml of blood was collected pre dose and 0·5, 1·0, 1·5, 2, 3h post dose, after which they u n d e r we n t a 4 h o u r h a e m o d i a l y s i s 60 Plasma Concentration (ng/ml) 50 40 30 Patient 1 Patient 2 20 10 Departments of Clinical Pharmacology and 2 Nephrology, Seth GS Medical College and KEM Hospital, Parel, Mumbai – 400012 Received: 11.06.2013; Accepted: 03.07.2013 1 © JAPI • august 2014 • VOL. 62 0 0 5 10 15 20 25 30 Time (hours) Fig. 1 : Plasma concentration versus time curve  767 108 Journal of the association of physicians of india • vol 62 • published on 1st of every month 1st august, 2014 Table 1 : Pharmacokinetic parameters in the 2 study patients Pharmacokinetic parameter Cmax (ng/ml) tmax (hr) AUC0-24 (ng-hr/ml) AUC0-∞ (ng-hr/ml) AUMC0-∞ (ng-hr-hr/ml) MRT (hr) Vd/F (l) Cl/F (l/hr) t1/2 (hr) Patient 1 47·8 3·0 291·3 291·3 1727·7 5·9 311·25 51·49 4·19 Patient 2 50·3 2·0 469·6 469·6 3199·9 6·8 316·55 31·94 6·87 session with the blood flow rate between 200 and 350 ml/min. Samples were further collected mid-dialysis (5 hours post dose) and at 8, 12, and 24 h post dose. Primaquine was measured by high performance liquid chromatography. 6 A concentration versus time curve for both the patients is depicted in Figure 1 and all the pharmacokinetic parameters (Table 1) were comparable to data from normal healthy individuals as reported in western countries 7,8 indicating that haemodialysis does not appear to alter the systemic exposure to a single oral dose (15 mg) primaquine in CKD patients and was well tolerated with no report of any adverse event. Acknowledgements The authors are grateful to Dr. Sanjay Oak, Director (ME and MHs), Seth GSMC and KEM Hospital, Mumbai for his support in conducting this study and the patients who gave consent to participate in the study. 768  Conflict of Interest The authors have no conflict of interest. References 1. Vinetz JM, Clain J, Bounkeua V, Eastman RT, Fidock D. Chemotherapy of Malaria. In: Brunton LL, Chabner BA, Knollmann BC, editors. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. New York: McGraw-Hill, 2011: 1409. 2. Vasson MP, Baguet JC, Arveiller MR, Bargnoux PJ, Giroud JP, Raichvarg D. Serum and urinary alpha-1 acid glycoprotein in chronic renal failure. Nephron 1993;65:299-303. 3. Wilairatana P, Westerlund EK, Aursudkij B, Vannaphan S, Krudsood S, Viriyavejakul P et al. Treatment of malarial acute renal failure by hemodialysis. Am J Trop Med Hyg 1999;60:233-37. 4. Tang TT, Phu NH, Vinh H, Hien TT, Cuong BM, Chau TT et al. Acute renal failure in patients with severe Falciparum malaria. Clin Infect Dis 1992;15:874-80. 5. KDOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification. Available at: http://www. kidney.org/professionals/kdoqi/guidelines_ckd/p4_class_g1.htm (accessed on 12 Apr 2012). 6. Dua VK, Kar PK, Sarin R, Sharma VP. High per formance liquid chromatographic determination of primaquine and carboxyprimaquine concentrations in plasma and blood cells in Plasmodium vivax malaria cases following chronic dosage with primaquine. Journal of Chromatography B 1996;675:93-98. 7. Mihaly GW et al. Pharmacokinetics of primaquine in man I. Studies of the absolute bioavailability and effects of dose size. Br J Clin Pharmacol 1985;19:745-750. 8. Ward SA et al. Pharmacokinetics of primaquine in man II. Comparison of acute vs chronic dosage in Thai subjects. Br J Clin Pharmacol 1985;19:751-755. © JAPI • august 2014 • VOL. 62