Sum maryTh is review present s bri efly th e resu lt s of a number of stu dies conducted In healt hy vo lun teers, designed to i nvestigate the pharmac okinetics of famc lclov i r. the oral form of the anti viral compound , pen ciclovir. These studies have show n th at famci clovi r is absorbed rap idly and extensive ly foll owing oral administration. Extens ive pre-sy stemi c metabolism of famcicl ovi r occ urs si nce co mpo und-related material in plasm a co nsists almost enti rely of deacetylaled and oxidize d metabol ites. little or no pare nt compound is detect ed In plasma or urine. The ma jo r metabolite of tamctctovtr is pencicl ovir. Maximum plasma co nce ntrations of pen cic tc vtr are ach ieved rap idl y foll ow ing ora l administration of ta mctcr cvrr, and total sys temic avail abilit y of penciclovi r is high (77%). Pharmacokl netl c paramete rs for penci clovir are lin ear over th e famcl clovi r oral dos e r ang e 125-750mg and the pencl clovl r Intravenous dose rang e 1O-20 mg kg-1 • The distribution of pencicl ovir afte r intravenous adminis tration Is consi ste nt wit h locali zation ou t of plas ma and Into ti ssues. Penc iclo vlr Is eli mi nated rapidl y and al most unchanged by net active tu bul ar secretion and glo merular filtrati on in th e kidn eys. The terminal pha se eli mi nation halfl ife of th e compound In healthy SUbjects is approximately 2 h. A study in health y elde rly male subje cts indi cated no cli nica lly signif icant effects of age on th e ph armacokinetics of penctct cvtr following oral f ameletovir adminis tration. Food appears to slo w the rate of ava ila bilit y of penclc lcvlr fr om oral tam crctcvr r, but has no effe cts on the ex tent of avai lability of p enclclovir. These data Ind icate that famciclovi r possesses exce lle nt pharm acokineti c prop erti es fo r t he provi sion of clinica lly u sef ul co ncen trations o f th e antiviral agen t penclclovir in the oral treatment o f herpesviral in fection s.

The plasma pharmacokinetics of pantoprazole have been investigated following single intravenous infusion and single oral administration at a dose of 40 mg to 12 healthy male subjects in a randomised cross-over study. Both treatments were generally well tolerated and no relevant compound-related adverse events were noted. The plasma pharmacokinetics of pantoprazole following intravenous infusion in this group of subjects were characterised by a total plasma clearance of 0.13 l.h-1 x kg-1 and apparent terminal elimination half-life 1.9 h. The apparent volume of distribution estimated at steady state (0.17 l.kg-1) was compatible with the localization of a major fraction of the compound in extracellular water. Following oral administration as an enteric-coated tablet formulation, a variable onset of absorption was followed by rapid attainment of maximum plasma concentrations of pantoprazole. Pantoprazole was well absorbed following oral administration; the absolute systemic bioavailability of the compound was estimated as 77% (95% CI, 67 to 89%).

Twenty healthy male volunteers received single oral doses of famciclovir (125-750 mg), in a randomized, single-blind, crossover study. Plasma and urine concentrations of penciclovir and its 6-deoxy precursor, BRL 42359, were determined and penciclovir plasma concentration-time data submitted to model-independent pharmacokinetic analysis. Peak plasma concentrations of penciclovir were obtained at median times of 0.5-0.75 h after dosing. The areas under the concentration versus time curves (AUC) and the peak penciclovir concentration (Cmax) increased linearly with dose of famciclovir. Time to Cmax, elimination half-life, urinary recovery and renal clearance of penciclovir did not change with increasing dose. Famciclovir was excreted via the kidneys as penciclovir (60%) and BRL 42359 (5%), respectively. Famciclovir was well tolerated by all subjects with a low incidence of adverse effects. In conclusion, penciclovir thus displays linear pharmacokinetics in the anticipated therapeutic dose range of famciclovir.

Consideration should be given to modification of the dosing schedule of famciclovir from the usual 8-hour interval to a 12-hour interval for patients with moderate renal impairment (CLCR 30 to 59 ml/min/1.73 m2) or a 24-hour interval for patients with severe renal impairment (CLCR < 30 ml/min/1.73 m2).