Subject steady-state

Pharmacokinetics Absorption is rapid, with peak plasma concentrations occurring in approximately 1 hour following oral administration in fasted subjects. Steady state is achieved after 2 days of multiple twice/day dosing. Levetiracetam is not extensively metabolized. The plasma half-life in adults is approximately 7 hours. Levetiracetam is eliminated from the systemic circulation by renal excretion. 

Following oral administration of 1 g four times a day to 8 subjects, steady-state plasma concentrations of 9.3 to 25.5 gg/ml (mean 18) were reported (A. J. Atkinson et a/., Clin. Pharmac. Ther., 1977,21, 575-587). 

Following daily oral administration of 300 mg to 7 subjects, steady-state serum concentrations of oxypurinol, determined immediately prior to a dose, were reported to range from 3.4 to 19.4 ig/ml (mean 9.7) (G. P. Rodnan et al., J. Am. med. 1975, 231, 1143-1147). 

Following oral administration of 300 mg daily in divided doses to 10 subjects, steady-state serum concentrations of 0.02 to 0.09pg/ml of amoxapine and 0.16 to 0.51 pg/ml of 8-hydroxyamoxapine were reported (W. E. Boutelle, Neuropharmacology, 1980,19, 1229-1231). 

Following oral administration of 50 mg three times a day to 9 subjects, steady-state plasma-butriptyline concentrations of 0.06 to 0.28 pg/ml (mean 0.15) were reported 6 hours after the final dose plasma concentrations of norbutriptyline were of a similar order (G. D. Burrows etal., Med. J. Aust., 1977,2, 604-606). 

Following single oral doses of 250 mg to 6 subjects, peak plasma concentrations of 23.9 to 39.4 pg/ml (mean 28) were attained in 1 to 7 hours. After daily oral doses of 250 to 500 mg to 4 subjects, steady-state plasma concentrations of 75.5 to 245.5 pg/ml (mean 142) were reported plasma concentrations of 4-chlorobenzenesulphonylurea and 2-hydroxy-chlorpropamide ranged from 3 to 6 pg/ml and < 1 to 9 ig/ml, respectively (J. A. Taylor, Clin. Pharmac. Ther., 1972, 75, 710-718). 

Following oral administration of 500 mg twice daily to 6 subjects, steady-state plasma concentrations of 66 to 183 pg/ml were reported (E. Wahlin- oWetal., Eur. J. din. Pharmac., 1981, 20, 375-378). 

Following daily oral doses of 20 mg of fluphenazine hydrochloride to 18 subjects, steady-state plasma concentrations of 0.0002 to 0.004 pg/ml were reported (J. I. Javaid fo/., J. chromatogr. Sd., 1981,19,439-443). 

After a single oral dose of 80 mg to 23 subjects, peak plasma concentrations of 0.7 to 4.9 pg/ml were attained in about 4 hours. Following daily oral administration of 80 mg to 144 subjects, steady-state plasma concentrations of 0.3 to 8.2 pg/ml (mean 2.5) were reported (D. B. Campbell et al.. Pharmacokinetics and Metabolism of Gliclazide, in Gliclazide and the Treatment of Diabetes, H. Keen et al. (Ed.), London, Royal Society of Medicine, 1980, pp. 71-82). 

Following daily oral doses of 25 mg to 8 subjects, steady-state plasma-guanethidine concentrations of 0.003 to 0.016 pg/ml (mean 0.009) were reported after oral doses of 37.5 mg daily to 8 subjects, the steady-state plasma-guanethidine concentrations ranged from 0.008 to 0.015 pg/ml (mean 0.011) (I. E. Walter Clin. Pharmac. Ther., 1975,18,571-580). 

Following daily oral doses of 2.5 mg to 6 subjects, steady-state plasma concentrations of 0.02 to 0.05 iig/ml (mean 0.03) were attained in 3 days (D. B. Campbell etal., Curr. med. Res. Opinion, 1977, 5, Suppl. 1, 13-24). 

Following daily oral doses of 150 mg given to 5 subjects, steady-state plasma concentrations of 0.08 to 0.22pg/ml (mean 0.13) were reported (G. H. Draffan et al., Br. J. din. Pharmac., 1976, 3, 489-495). 

Following a single oral dose of 600 mg to 10 subjects, peak plasma concentrations of 0.45 to 0.80 mmol/litre (mean 0.64) were attained in about 2 hours (J. M. Meinhold etal., J. din. Pharmac.,-1979,19,701-703). After daily oral doses of 1.5 to 1.7 g to 16 subjects, steady-state serum concentrations were in the range 0.7 to 0.9 mmol/litre (J. L. Marini and M. H. Sheard, J. din. Pharmac., 1976,16, 276-283). 

After a single oral dose of 50 mg to 1 subject, peak concentrations of 19.1 and 0.08 pg/ml in blood and plasma respectively were reported at 3 hours the corresponding concentrations, 3 hours after a dose of 150 mg to a different subject were 36.1 and 1.4 pg/ml. Following oral doses of 100 mg three times a day to 1 subject, steady-state concentrations of about 40 pg/ ml and about 9.5 pg/ml were reported for blood and plasma respectively (W. F. Bayne eta/., ibid.). 

Following daily oral doses of 300 to 400 mg to 4 subjects, steady-state plasma concentrations of 0.05 to 0.14 pg/ml (mean 0.08) were reported steady-state plasma concentrations of the sulphoxide metabolite ranged from 0.26 to 0.39pg/ml (mean 0.33) the V-monodesmethyl metabolite was also detected (S. G. Dahl and M. Garle, J. pharm. Set, 1977,66,190-193). 

Following daily oral doses of 60 to 600 mg to 11 subjects, steady-state plasma concentrations of 0.2 to 1.7 pg/ml (mean 0.9) of methylphenobar-bitone and 4 to 32 pg/ml (mean 15) of phenobarbitone were reported (H. J. Kupferberg and J. Longacre-Shaw, Ther. Drug Monit., 1979, 1, 117-122). 

During constant intravenous infusion of 0.02 mg/min to 3 subjects, steady-state plasma concentrations of 0.014, 0.015 and 0.030 pg/ml were reported (E. F. Hahn etal., J. Pharm. Pharmac., 1983, 35, 833-836.)... 

Following a single oral dose of 5 mg to 9 subjects, peak plasma concentrations of 0.028 to 0.045 pg/ml (mean 0.04) were attained in 0.5 to 4 hours (D. D. Breimerer a/.,. fir. J. din. Pharmac., 1911, 4, 709-711). Following daily oral doses of 5 mg to 4 subjects, steady-state plasma-nitrazepam concentrations of 0.035 to 0.044 pg/ml (mean 0.04) were reported combined steady-state concentrations of the, 7-amino and 7-acetamido metabolites were in the range 0.018 to 0.053 pg/ml (mean 0.03) (J. Rieder and G. Wendt, Pharmacokinetics and Metabolism of the Hypnotic Nitrazepam, in The Benzodiazepines, S. Garattini, E. Mussini and L. O. Randall (Ed.), New York, Raven Press, 1973, pp. 99-127). 

After a single intravenous dose of 0.5 mg to 3 subjects, a plasma concentration of about 0.012 pg/ml was reported in 5 minutes following daily intravenous administration of 0.25 mg to 3 subjects, steady-state plasma concentrations of about 0.0005 pg/ml were attained on the 4th or 5th day (R. Selden and T. W. Smith, ibid.). 

Following daily oral doses of 300 to 400 mg to 6 subjects, steady-state plastna concentrations determined immediately before a dose ranged from 27 to 95 ig/ml (mean 62) (M. Weiner et al., Proc. Soc. exp. Biol. Med., mi, 72, 1170-1173). 

Following daily oral doses of 8 to 19 mg/kg (mean 12) to 5 subjects, steady-state serum concentrations of 0.5 to 2.5 pg/ml (mean 1.8) of quinidine, 0.38 to 0.94pg/ml (mean 0.55) of 3-hydroxyquinidine, and 0.02 to 0.12 pg/ml (mean 0.07) of quinidin-2 -one, were reported following daily oral doses of 8.6 to 13.3 mg/kg (mean 10.7) to 8 subjects with mild renal dysfunction, steady-state serum-quinidine concentrations ranged from 1.4 to 3.6 ig/ml (mean 2.3) (D. E. Drayer et al., Clin. Pharmac. Ther., 1978,24,31-39). 

After daily oral doses of 4 g to 9 subjects, steady-state serum concentrations of 37 to 92 pg/ml (median 50) for total sulphapyridine and its metabolites,... 

Following oral administration of 50 mg, three times a day to 14 subjects, steady-state plasma concentrations of 0.03 to 0.6 pg/ml (mean 0.18) were reported, 4 to 7 hours after the final dose (J. K. Salminen etal., Curr. ther. Res., mo, 27,109-115). 

Following a single oral dose of 150 mg to 4 subjects, mean peak plasma concentrations of 2.05 ig/ml of trazodone and 0.01 ig/ml of l-(3-chlorophenyOpiperazine were reported at about 2 hours and 2 to 4 hours, respectively (S. Cacciaeta/., J. Phartn. Pharmac., 1982,34, 605-606). Following oral administration of 25 mg three times a day to 10 subjects, steady-state serum concentrations averaged 0.7 ig/ml on the twelfth day (B. Catanese et al.. Boll, chim.-farm., 1978, 777,424-427). 

Following chronic oral doses of 80 mg 6-hourly to 16 subjects, steady-state trough plasma concentrations of 0.031 to 0.168 pg/ml (mean 0.105) of verapamil, and 0.078 to 0.279 pg/ml (mean 0.171) of norverapamil were reported maximum steady-state plasma concentrations were 0.135 to 0.447 pg/ml (mean 0.255) and 0.134 to 0.361 pg/ml (mean 0.226) for verapamil and norverapamil respectively, attained 1 hour after a dose (S. B. Freedman era/., Clin. Pharmac. Ther., 1981,30,644-652). 

Following oral doses averaging 225 mg daily, given twice a day to 8 subjects, steady-state plasma concentrations of 0.029 to 0.102 pg/ml (mean 0.07) of zimeldine and 0.145 to 0.554 pg/ml (mean 0.25) of norzimeldine were reported. The corresponding steady-state concentrations in cerebrospinal fluid were 0.003 to 0.007 (mean 0.006) and 0.027 to... 

Tenofovir In an open, three-period study of the interaction of tenofovir disoproxil fumarate 300 mg/day with either fosamprenavir 1400 mg bd or fosamprenavir + ritonavir 700/100 mg for 14 days in 36 healthy subjects, steady-state plasma amprenavir and tenofovir pharmacokinetics were minimally or not significantly altered [170 ]. 

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