Pharmacokinetics ofFoscarnet andDistribution toCerebrospinal Fluid after Intravenous Infusion inPatients withHuman Immunodeficiency Virus Infection

Toinvestigate thepharmacokinetics andeffects ofintravenous foscarnet, 13relatively healthy malepatients withhumanimmunodeficiency virus infection anda mean CD4+lymphocyte value of0.45x 10-9cells perliter were given acontinuous intravenous infusion offoscarnet (0.14 to0.19mg/kg permin)for8to21days. Blood andurinesamples were takenduring andafter drugadministration tomonitor foscarnet concentrations. Lumbarpuncture was performed during theinfusion infive patients. Theconcentrations inplasma showed large variations bothwithin andbetween patients. Thedisposition offoscarnet couldbeexplained bya triexponential equation (tl2,1, 0.40to2.52h;t112X, 3.20to16.7h;tl/2J3, 36to196h).Renalclearance accounted formostoftheplasma clearance, thedilerence probably reflecting thepassageoffoscarnet into bone.Upto20%ofthecumulative dosemay havebeendeposited inbone7dayspostinfusion. Foscarnet was distributed tothecerebrospinal fluid ina concentration varying from13to68% ofthesimultaneous concentration inplasma. Polyuria andpolydipsia were recorded inallpatients. Thereappearstobean association between thedegree ofmalaise, including symptomssuchas nausea,vomiting, fatigue, and headache, andconcentrations inplasma above350,umol/liter.