Foscarnet pharmacokinetics

Aweeka FT, Jacobson MA, Martin-Munley S, et al. Effect of renal disease and hemodialysis on foscarnet pharmacokinetics and dosing recommendations. J Acquir Immune Defic Syndr Hum Retrovirol 1999 20 348-347. 

Pharmacokinetics Foscarnet is 14% to 17% bound to plasma protein at plasma drug concentrations of 1 to 1000 mcM. 

Detailed pharmacokinetic studies were performed on transscleral iontophoresis of various drugs [38-40,42,75-78]. Each drug resulted in different patterns of distribution in the vitreous. Carboplatin distribution in the vitreous after iontophoretic delivery demonstrated heightened levels in a controlled manner from 1 to 6 h after treatment [39], Foscarnet iontophoresis demonstrated a very low elimination rate, thus therapeutic levels in the vitreous were maintained for up to 60 h [78]. Methylprednisolone obtained a relatively low peak concentration 2 h after treatment [38], and gentamicin showed a peak concentration 16 h after the transscleral iontophoresis [42]. 

Wagstaff AJ, Bryson HM (1994) Foscarnet A reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic use in immunocompromised patients with viral infections. Drugs 48 153-205. 

Ringden O, Lonnqvist B, Paulin T, Ahimen J, Klintmalm G, Wahren B, Lernestedt J-0. Pharmacokinetics, safety and preliminary clinical experiences using foscarnet in the treatment of cytomegalovirus infections in bone marrow and renal transplant recipients. J Antimicrob Chemother 1986 17 373-387. 

Berthe P, Baudouin C, Garraffo R, et al. Toxicologic and pharmacokinetic analysis of intravitreal injections of foscarnet, either alone or in combination with ganciclovir. Invest Ophthalmol Vis Sci 1994 35 1038-1045. 

Pharmacokinetics Foscarnet is given intravenously and penetrates well into tissues, including the CNS. Up to one-third of a dose may be deposited in bone. The drug undergoes renal elimination in direct proportion to creatinine clearance. 

No pharmacokinetic interactions occur between foscarnet and di-danosine, zalcitabine or zidovudine. The UK manufacturer does not recommend the concurrent use of lamivudine and foscarnet... 

Intravenous foscarnet 90 mg/kg every 12 hours and oral zalcitabine 750 micrograms every 8 hours were given to 12 HIV-positive subjects for 2 days. There were no clinically significant alterations in the pharmacokinetics of either drug. However, the manufacturers of zalcitabine suggested that the concurrent use of zalcitabine and foscarnet should be well monitored, because foscarnet may possibly decrease the renal elearanee of the zalcitabine, thereby increasing its serum levels and its toxicity, particularly peripheral neuropathy. The antiretroviral effects of foscarnet and zalcitabine were synergistic. ... 

The antiviral effects of foscarnet and zidovudine appear to be additive or synergistic. No significant alteration in the pharmacokinetics of either drug was seen in a 14-day study in 5 AIDS patients given both drugs. Foscarnet does not appear to affect zidovudine intracellular activation, and the manufacturer notes that there was no evidence of increased myelotoxicity when foscarnet was used with zidovudine. No special precautions are required on concurrent use. 

Aweeka FT, Brody SR, Jacobson M, BotwinK, Martin-Munley S. Is tiiere a pharmacokinetic interaction between foscarnet and citabine during concomitant administration Clin Ther (1998) 20, 232-43. 

Hivid (Zalcitabine). Roche Pharmaceuticals. US Prescribing information, September 2002. Aweeka FT, Gambertoglio JG, van der Horst C, Raasch R, Jacobson MA. Pharmacokinetics of concomitantiy administered foscarnet and zidovudine for treatment of human immunodeficiency virus irifection (AIDS clinical trials group protocol 053). Antimicrob Agents Chem-other(l992)36,1773-8. 

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