Renal dialysis pharmacokinetics

The risk of clinically relevant drug interactions is minimal with S-(-)-levetiracetam, because it does not alter the pharmacokinetics of coadministered drugs by inhibition or induction of hepatic enzymes (84). Toxic effects include mild to moderate somnolence, asthenia, ataxia, and dizziness these effects seldom require discontinuance. An increase in the incidence of behavioral abnormalities in children and in adults having a previous history of neuropsychiatric problems has been noted (85). Its use in the elderly or in patients with renal Impairment will require an individualization of dose, and an additional dose is needed after renal dialysis. Levetiracetam was associated with developmental toxicity in the offspring of pregnant animals. 

In children from 4 to 17 years of age, topiramate exhibits linear pharmacokinetics, with a 50% increase in clearance rate compared to adults (95). Topiramate may require up to a 50% dose reduction in patients with renal insufficiency, and a replacement dose may be needed after renal dialysis. Topiramate has demonstrated teratogenicity in animal studies. 

Pharmacokinetics Rapidly and completely absorbed from the GI tract. Protein binding less than 36%. Widely distributed (crosses the blood-brain barrier). Primarily excreted unchanged in urine. Not removed by hemodialysis or peritoneal dialysis. Half-life II-I5 hr (intracellular), 2-11 hr (serum, adults), 1.7-2 hr (serum, children). (Increased in impaired renal function). 

Joffe, R, Thomsen, H.S., and Meusel, M. (1998) Pharmacokinetics of gadodiamide injection in patients with severe renal insufficiency and patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis. 

Brody SR, Humphreys MH, Gambertoglio JG, Schoenfeld P, Cundy KC, Aweeka FT. Pharmacokinetics of cidofovir in renal insufficiency and in continuous ambulatory peritoneal dialysis or high-flux hemodialysis. Clin Pharmacol Ther 1999 65(l) 21-8. 

Eriksson T, Hoglund P, Turesson I, Waage A, Don BR, Vu J, Scheffler M, Kaysen GA. Pharmacokinetics of thalidomide in patients with impaired renal function and while on and off dialysis. J Pharm Pharmacol 2003 55(12) 1701-6. 

It has been recommended that the dosing interval of pentamidine be extended to 48 hours for patients with a GFR less than 10 ml/min [173] and that there is no need for dosing after hemo or peritoneal dialysis. However, Conte in his report [141], suggested that dose reduction of pentamidine for renal impairment is unnecessary and noted that while his patients had mild to moderate PCP, it remains unknown whether the pharmacokinetics of pentamidine might be altered in more severely ill patients. 

In patients with mild to moderate and severe kidney impairment, peak plasma levels of fexofenadine were 87% and 111% greater, respectively, and mean elimination half-lives were 59% and 72% longer, respectively, than observed in normal volunteers. Peak plasma levels in patients on dialysis were 82% greater and half-life was 31% longer than observed in normal volunteers. Based on increases in bioavailability and half-life, a dose of 60 mg once daily is recommended as the starting dose in patients with decreased renal function. The pharmacokinetics of fexofenadine hydrochloride in patients with hepatic disease did not differ substantially from that observed in healthy patients. 

Treatment of the adverse effects of PCP is difficult for several reasons. PCP has a very high volume of distribution (6.2 liters per kilogram (L/kg) in humans) and its clearance is primarily by metabolism (Cook et al. 1982) with only a small contribution from renal excretion. Its major sites of action in the central nervous system (CNS) are far removed from the beneficial effects of most traditional treatment methods such as dialysis. In addition, there is no specific antagonist for PCP s adverse effects. These pharmacokinetic and receptor-medicated characteristics make it very difficult to develop effective treatment strategies. Some of the current methods for treatment of overdose are urine acidification, diazepam administration to control convulsions (Aronow and Done 1978 ... 

Sica DA, Gehr TW. The pharmacokinetics of angiotensin-converting enzyme inhibitors in end-stage renal disease. Semin Dialysis 1994 7 205-213. 

Matzke GR, Comstock TJ. Influence of renal disease and dialysis on pharmacokinetics. In Applied Pharmacokinetics Principles of Therapeutic Drug Monitoring, 4th ed. Evans WE, Schentag 11, Burton ME (eds.). Baltimore, Lippincott Williams and Wilkins, 2005. 

Interferon-o, a 165 amino acid glycoprotein, is effective in the treatment of viral hepatitis C and B, myeloma, melanoma, and renal carcinoma. Little is known about the renal metabolism of interferon-a despite extensive studies in experimental animals. In patients with normal renal function, the serum peak level occurs 8 hours after a subcutaneous injection of 3x10 units of interferon-a. Terminal elimination half-life ranges from 4 to 16 hours and after 24 to 48 hours, the interferon molecule is undetectable in the serum [181]. A-interferon urinary level is undetectable. Some authors have suggested that, despite the lack of urinary excretion, the kidney could play a role in interferon-a metabolism [182]. Indeed, as far as hepatitis C treatment is concerned, dialysis patients often show a better response to therapy than non-dialysis patients. This better efficacy in dialysis patients is associated with an increase of the incidence of adverse effects. This observation raises the question of pharmacokinetic modifications. One study documented that clearance kinetics of interferon-a in patients with chronic renal failure are about half the rate of patients with normal renal function [183]. Indeed interferon is filtered by the glomeruli and largely absorbed and catabolized within tubular cells [184]. 

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