Steady-state serum concentration

The steady-state serum concentrations of a patient taking gentamycin were found to be 10 mcg/mL (Cmax ss) and 2.5 mcg/mL (Cmin The patient was taking the usual dose of 3 mg/kg/day of gentamycin. Would you recommend a change in dosing schedule If so, how ... 

Although itraconazole and fluconazole are both triazoles, they are chemically and pharmacologically distinct. Itraconazole (Sporanox) is lipophilic and water insoluble and requires a low gastric pH for absorption. Oral bioavailability is variable, only 50 to 60% when taken with food and 20% or less when the drug is taken on an empty stomach. Itraconazole is highly protein bound (99%) and is metabolized in the liver and excreted into the bile. With initial dosing, the plasma half-life is 15 to 20 hours steady-state serum concentrations are reached only after 2 weeks of therapy, when the half-life is extended to 30 to 35 hours. In lipophilic tissues, drug concentration is 2 to 20 times that found in... 

Nonlinear relationship of phenytoin dosage and plasma concentrations. Five patients (identified by different symbols) received increasing dosages of phenytoin by mouth, and the steady-state serum concentration was measured at each dosage. The curves are not linear, since, as the dosage increases, the metabolism is saturable. Note also the marked variation among patients in the serum levels achieved at any dosage. 

Foscarnet is available in an intravenous formulation only poor oral bioavailability and gastrointestinal intolerance preclude oral use. Cerebrospinal fluid concentrations are 43-67% of steady-state serum concentrations. Although the mean plasma half-life is 3-6.8 hours, up to 30% of foscarnet may be deposited in bone, with a half-life of several months. The clinical repercussions of this are unknown. Clearance of foscarnet is primarily renal and is directly proportional to creatinine clearance. Serum drug concentrations are reduced approximately 50% by hemodialysis. 

Relationships between serum infliximab concentrations and clinical improvements in RA were also examined recently [79]. Following the administration of 3 and 10 mg/kg doses every eight to 10 weeks, dose-proportional increases in maximum steady-state serum concentrations (Cmax) of the antibody were evident. Considerable variability in the trough serum concentrations (Cmin) of the antibody was observed. The highest proportion of response (ACR50 and ACR70) was re-... 

The population PK/PD of efalizumab were recently evaluated in patients with moderate to severe plaque psoriasis following SC administration of 1.0 and 2.0 mg/kg for 12 weeks [81-83]. Steady-state serum concentrations were achieved by four to eight weeks following administration of 1 and 2 mg/kg doses, respectively. At both doses, CDlla expression on T lymphocytes was reported to be maximally down-modulated. In addition, at doses of 1 and 2 mg/kg, >95 % of CDlla binding-sites were reported to be saturated at steady-state serum trough concentrations of 9 and 24 pg/mL, respectively. The improvement in PAS I scores was observed quickly, and efalizumab administration was reported to result in 60-70% improvement in PASI scores when compared to baseline after 12 weeks of treatment. The current recommended dose for efalizumab is a single 0.7 mg SC conditioning dose which is followed by weekly SC doses of 1 mg/kg. 

A therapeutic target range for serum risperidone concentrations has not been established, but in 20 of 22 patients taking 6 mg/day, which is considered the optimum dosage for most patients, risperidone serum concentrations were 50-150 nmol/1 (278). Steady-state serum concentrations of risperidone and 9-hydroxyrisperidone, the active moiety, were also measured in 42 patients there was no correlation between the serum concentration of the active moiety and adverse effects. 

The effects of concomitant carbamazepine, phenytoin, sodium valproate, and zonisamide on the steady-state serum concentrations of clonazepam have been investigated in 51 epileptic in-patients under 20 years of age (14). Serum concentrations of clonazepam correlated positively with the dose of clonazepam and negatively with the doses of carbamazepine and valproic acid, but not with phenytoin or zonisamide. These results confirm that as the oral doses of carbamazepine and sodium valproate increase, the serum concentration of clonazepam falls, but there is no interaction with either phenytoin or zonisamide. In the case of carbamazepine the mechanism of action is thought to be enzyme induction, increasing the metabolism of clonazepam. It is not known what the mechanism is with sodium valproate. In patients with epilepsy, the co-administration of either sodium valproate or carbamazepine will reduce the serum concentration of clonazepam and increase the risk of a seizure. When... 

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). 

Steady-state serum concentrations of 4.7 to 32.4 pg/ml (mean 11.5) were reported in 7 subjects receiving chronic treatment with oral doses of 1 g daily (F. T. Murray etal., J. din. Pharmac., 1979,19, 704-711). 

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). 

A mean minimum steady-state serum concentration of 0.004 pg/ml of clopenthixol was reported in 24 subjects, who had been receiving average doses of 200 mg intramuscularly every 4 weeks, for 5 to 6 months (S. J. Denckerer a/., Actapsychiat. scand., 1980,61, Suppl. 279, 55-63). Following an oral dose of 30 mg of clopenthixol to 1 subject, a peak serum concentration of about 0.005 pg/ml of d -clopenthixol was attained in about 3 hours the peak concentration of the inactive /ra/i5-isomer was slightly higher and was attained after 4 hours the serum concentrations declined slowly and were still measureable after 48 hours only traces of the des-(2-hydroxyethyl) metabolite were detected (T. Aaes-Jorgensen, J. Chromat., 1980,183 Biomed. AppL, 9, 239-245). 

Average steady-state serum concentrations of 0.40 to 0.61 gg/ml (mean 0.48) of desmethyldiazepam were reported in 7 patients receiving daily oral doses of 0.6 mg/kg (A. J. Wilensky et al., Clin. Pharmac. Ther., 1978, 24, 22-30). 

Steady-state serum concentrations of 31 to 68pg/ml (mean 49) were reported in 5 young adults receiving daily oral doses of 1 g (E. B. Solow and J. B. Green, Clinica chim. Acta, 1971, 33, 87-90). 

Steady-state serum concentrations of 0.0008 to 0.033 ig/ml (mean 0.0065) were attained after daily oral administration of 1 to 14 mg (mean 6) to 34 patients (A. O. Forsman and R. Ohman, Curr. ther. Res., 1977, 21, 396-411). 

Following intravenous infusions at rates varying between 20 and 50 pg/min/kg to 24 subjects, the following steady-state serum concentrations... 

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). 

A mean steady-state serum concentration of 26 pg/ml of total hydantoin was reported for 173 subjects receiving daily oral doses averaging 6.8 mg/ kg methoin concentrations averaged 8% of the total hydantoin concentration (A. S. Troupin etai. Epilepsia, 1976,17,403-414). 

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 choline salicylate, equivalent to 3.8 g of aspirin, a mean steady-state serum concentration of 166 pg/ml was reported (P. 

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 daily oral doses of 20 mg to 10 subjects for 6 days, trough steady-state serum concentrations of 0.017 to 0.132pg/ml (mean 0.05) were reported (H. R. Ochs et al., J. din. Pharmac., 1984,24, 58-64). 

Following daily oral doses of 6.9 to 18.2 mg/kg of aminophylline to 14 subjects, trough steady-state serum concentrations of 6.6 to 15iJ.g/ml (mean 11) were reported in the morning, in comparison with trough serum concentrations of 5.0 to 13 pg/ml (mean 9.6) in the afternoon (L. J. Lesko et al., J. pharm. Sci., 1980,69, 358-359). 

Following daily oral administration of 300 mg twice a day to 6 subjects, maximum steady-state serum concentrations of 18.6 to 73.3 ig/ml (mean 48) were reported 0.5 to 1.5 hour after a dose (T. J. Daymond 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). 

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