Nevirapine

PD Dialyzability: Likely

Pharmacokinetic Parameters [1] [2] [3]

	Nevirapine
Molecular Weight (Da)	266.3
Plasma Protein Binding (%)	50 - 60
Volume of Distribution (L/Kg)	1.2 - 1.4
Hepatic Metabolism	> 95% metabolism via CYP3A4 (major), CYP2B6 (minor)
Excreted Unchanged (%)	< 3
Half-Life; Normal Renal Function (hours)	23
Half-Life; ESRD (hours)	23

CAPD/CCPD Dosing:

No large studies are available to provide dosing recommendations for nevirapine in PD patients. Two case reports suggest nevirapine 200 mg PO BID can be recommended in the PD population [4] [5]. However, given extensive hepatic metabolism and minimal renal elimination of unchanged drug, it is unlikely that dosage adjustment is required.

Literature Summary:

Title	Patient	Intervention	Outcome	Note
Pharmacokinetics of nelfinavir and nevirapine in a patient with end-stage renal failure on continuous ambulatory peritoneal dialysis [4]	34 year old HIV postive female. CrCl < 10 mL/min. ESRD secondary to chronic pyelonephritis on CAPD.	Nevirapine 200mg BID + nelfinavir 1250mg BID + zidovudine 250mg BID	Concentrations in dialysate were ~50% of those in plasma Approximately 16 mg of nevirapine lost through dialysate in 24-hour period. Following 12 weeks of treatment: CD4+ (x103 cells/L): 110🡪 240 Viral load (RNA copies/mL): 88000 at baseline 🡪 <50 Plasma trough concentrations were similar to those found in study where patients received nevirapine 200mg once daily.	No adverse effects reported over 16 weeks
Pharmacokinetics of ritonavir and nevirapine in peritoneal dialysis [5]	40 year old HIV positive male. On CAPD, ESRD secondary to HIV-associated nephropathy	Nevirapine 200mg q12h + ritonavir 600mg q12h + zidovudine 100mg q8h + didanosine 100mg q24h	No change in PK parameters in comparison to normal renal function, except AUC was increased. Extraction ratio (%): 51.9% PD Clearance (ml/min): 3.3mL/min	No adverse effects seen during study

References

[1]	Foisy M, Tseng A. Selected properties of nevirapine. Immunodeficiency clinic [Internet]. 2014 Dec [cited 2018 Feb 25]. 1-8. Available from www.hivclinic.ca.

[2]	Wishart DS, Knox C, Guo AC, Shrivastava S, Hassanali M, Stothard P, et al. Drugbank: a comprehensive resource for in silico drug discovery and exploration. Nucleic Acids Res. 2006 Jan 1: 34(database issue):D668-672.

[3]	Adult Drug Book. Kidney Disease Program [Internet]. Unknown [cited 2018 Feb 20]. Available from: https://kdpnet.kdp.louisville.edu/drugbook/adult/

[4]	(1, 2) Taylor S, Little J, Halifax K, Drake S, Back D. Pharmacokinetics of nelfinavir and nevirapine in a patient with end-stage renal failure on continuous ambulatory peritoneal dialysis. J Antimicrob Chemother 2000;45(5):716-717.

[5]	(1, 2) Izzedine H, Launay-Vacher V, Deray G. Pharmacokinetics of ritonavir and nevirapine in peritoneal dialysis. Nephrol Dial Transplant 2001;16(3):643.