Steady-state plasma concentration average

Figure 5.2 Plasma concentration curve of drug after single and repeated administration Csj. nax, maximal steady-state plasma concentration after repeated administration Css av, average steady-state concentration after repeated administration Css mm- minimal steady-state concentration after repeated administration n. maximal plasma concentration after single oral dose t Inax. time to maximal concentration after single oral dose t plasma half-life after single oral dose AUC, area under the concentration vs. time curve...

After intravenous administration of 175 mg/70 kg to five individuals, the average peak serum concentration was 1.0 mg/L achieved at 12 min.2 The concentration declined by 50% within 30 min. The plasma half-life is reported to be 3 to 4 h with a volume of distribution of 3 to 5 L/kg.1 Continuous infusion of 41 pg/kg/min after a 2-mg/kg bolus produced an average (n = 31) steady-state plasma concentration of 2.2 mg/L.3... 

Peak plasma concentrations of 0.010 to 0.026 pg/ml (mean 0.018) were reported 3 hours after administration of a single oral dose of 150 mg to 6 subjects (L. E. Hollister eta/., Clin. Pharmac. Ther., 1970,11, 49-59). Following daily oral doses of 200 to 600 mg to 10 subjects, minimum steady-state plasma concentrations of 0.002 to 0.122 pg/ml (mean 0.03) of chlorpromazine were reported monodesmethylchlorpromazine and 7-hydroxychlorpromazine plasma concentrations averaged 16% and 30% respectively of the chlorpromazine plasma concentration, but there were considerable intersubject variations (G. Alfredsson etal. Psychopharmacology, 1976,4< , 123-131). 

Following oral daily doses averaging 6 mg/kg to 63 subjects, mean steady-state plasma concentrations of 3.3 pg/ml for disopyramide and 0.99 pg/ml for the desalkyl metabolite were reported plasma concentrations were higher in 17 subjects with renal dysfunction (mean 4.3), but lower in subjects concurrently taking enzyme-inducing drugs (M. Aitio, Br. J. din. Pharmac., 1981,11, 369-376). 

During continuous intravenous infusion at an average rate of 41 ig/kg/ minute to 31 subjects, a mean steady-state plasma concentration of 2.2 pg/ ml was reported norketamine and dehydronorketamine attained mean peak plasma concentrations of 1.1 pg/ml and 0.7 pg/ml, respectively, in about 3 hours the subjects awoke at an average plasma concentration of 0.64 pg/ml (J. Idvall et al., Br. J. Anaesth., 1979, 51,1167-1173). Following an intramuscular injection of 0.5 mg/kg to 6 subjects, peak plasma concentrations of 0.10 to 0.43 pg/ml (mean 0.24) were attained in about 0.3 hour norketamine attained a mean peak plasma concentration of 0.09 pg/ml at about 1 hour (J. A. Clements et al., J. pharm. Sci., 1982, 71, 539-542). 

Following oral administration of 200 mg twice daily to 9 subjects, average steady-state plasma concentrations of 0.04 to 0.18 lag/ml (mean 0.09) were reported (J. J. McNeil et al., Br. J. din. Pharmac., 1982,13, Suppl. 1,75S-80S). 

Following a single oral dose of 2 g to 8 subjects, peak plasma concentrations of 7 to 32 pg/ml (mean 17) of sulphasalazine were attained in about 3 hours peak plasma concentrations of sulphapyridine averaged about 20 pg/ml (E. M. Ryde and J. J. Lima, Curr. ther. Res., 1981,29, 728-737). Following daily oral doses of 3 g to 6 subjects, minimum steady-state plasma concentrations of 0.04 to 0.34 pg/ml of 5-aminosalicylic acid and... 

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 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... 

After a single oral dose of 100 mg to 21 subjects, peak plasma concentrations averaged 4.7 pg/ml at about 1 hour following oral administration of 100 mg four times a day to 10 subjects, steady-state plasma concentrations of about 3 to 4 pg/ml were reported (R. K. Nayak etal., Clin. Pharmac. Ther., 1980, 27, 395-401). 

Assuming knowledge of the systemic clearance and the desired average steady-state plasma concentration of a drug, the dosage rate can be calculated from... 

Systemic clearance, which measures the ability of the body to eliminate a drug, determines the relationship between the dosage rate and the average steady-state plasma concentration. When multiple (fixed) doses of a drug are administered at a constant dosage interval (r) the average plasma concentration that will be attained at steady-state can be predicted ... 

Unlike the estimates of dosage rates and average steady-state plasma concentrations, which may be determined independently of any pharmacokinetic model in that systemic clearance is the only pharmacokinetic parameter used, the prediction of peak and trough steady-state concentrations requires pharmacokinetic compartmental model assumptions. It is assumed that, (i) drug disposition can be adequately described by a one-compartment pharmacokinetic model, (ii) disposition is independent of dose (i.e. linear pharmacokinetics apply), and (iii) the absorption rate is much faster than the rate of elimination of the drug, which is always valid when the drug is administered intravenously. For clinical applications, these assumptions are reasonable. 

What maintenance dose should be administered intravenously every 6 hours to eventually obtain average steady-state plasma concentrations of 4 mg/L ... 

The "average" steady-state plasma concentration, (Cp)ss, for an intravenous bolus dose and for an extravascular dose. 

In a normal subject, systemic clearance of a drug is constant and it is presumed to be independent of the dose administered and the route of administration therefore, it will not play any role in influencing the "average" steady-state concentration. The "average" steady-state plasma concentration will be influenced by the three remaining parameters the dose administered, the chosen dosing interval and the absolute bioavailability (F), when applicable. 

What average steady-state plasma concentration (Cp)ss would be obtained ... 

The dosage regimen of 250 mg every 4h will provide an average steady-state plasma concentration of 24.80 mg L which is quite close to 26 mgL b... 

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