Lack of kinetic interaction between valproic acid and citrus pectin.

To determine the influence of ingestion of dietary fiber (citrus pectin) in the kinetic disposition of valproic acid, two studies were conducted in adult volunteers. Twelve healthy subjects took single oral doses of 500 mg valproic acid in a form of sodium valproate as coated tablets, on two occasions: under fasting conditions (treatment A) or immediately after ingestion of 14 g citrus pectin (treatment B). In each study, a randomized, single-dose, two-way crossover design was used, and 8 days elapsed between the two trials. Assays were carried out for valproic acid in plasma samples, which were collected from zero to 48 hours after drug administration. The peak plasma concentration (60.52 vs. 55.74 micrograms x ml-1), the time to peak concentration (3.47 vs. 3.91 h), the absorption rate constant (0.12 vs. 0.12 h-1), and the area under the plasma concentration-time curve (1324.0 vs. 1268.5 micrograms x h x ml-1) did not differ significantly between treatments A and B (median, Wilcoxon test). These results suggest that the administration of citrus pectin does not alter the rate and extent of absorption of valproic acid administered as a single dose to healthy volunteers.

Diclofenac plasma protein binding: PK-PD modelling in cardiac patients submitted to cardiopulmonary bypass.

Twenty-four surgical patients of both sexes without cardiac, hepatic, renal or endocrine dysfunctions were divided into two groups: 10 cardiac surgical patients submitted to myocardial revascularization and cardiopulmonary bypass (CPB), 3 females and 7 males aged 65 +/- 11 years, 74 +/- 16 kg body weight, 166 +/- 9 cm height and 1.80 +/- 0.21 m2 body surface area (BSA), and control, 14 surgical patients not submitted to CPB, 11 female and 3 males aged 41 +/- 14 years, 66 +/- 14 kg body weight, 159 +/- 9 cm height and 1.65 +/- 0.16 m2 BSA (mean +/- SD). Sodium diclofenac (1 mg/kg, im Voltaren 75 twice a day) was administered to patients in the Recovery Unit 48 h after surgery. Venous blood samples were collected during a period of 0-12 h and analgesia was measured by the visual analogue scale (VAS) during the same period. Plasma diclofenac levels were measured by high performance liquid chromatography. A two-compartment open model was applied to obtain the plasma decay curve and to estimate kinetic parameters. Plasma diclofenac protein binding decreased whereas free plasma diclofenac levels were increased five-fold in CPB patients. Data obtained for analgesia reported as the maximum effect (EMAX) were: 25% VAS (CPB) vs 10% VAS (control), P < 0.05, median measured by the visual analogue scale where 100% is equivalent to the highest level of pain. To correlate the effect versus plasma diclofenac levels, the EMAX sigmoid model was applied. A prolongation of the mean residence time for maximum effect (MRTEMAX) was observed without any change in lag-time in CPB in spite of the reduced analgesia reported for these patients, during the time-dose interval. In conclusion, the extent of plasma diclofenac protein binding was influenced by CPB with clinically relevant kinetic-dynamic consequences.

Diclofenac plasma protein binding: PK-PD modelling in cardiac patients submitted to cardiopulmonary bypass

Twenty-four surgical patients of both sexes without cardiac, hepatic, renal or endocrine dysfunctions were divided into two groups: 10 cardiac surgical patients submitted to myocardial revascularization and cardiopulmonary bypass (CPB), 3 females and 7 males aged 65 ñ 11 years, 74 ñ 16 kg body weight, 166 ñ 9 cm height and 1.80 ñ 0.2l m2 body surface area (BSA), and control, 14 surgical patients not submitted to CPB, 11 female and 3 males aged 41 ñ 14 years, 66 ñ 14 kg body weight, 159 ñ 9 cm height and 1.65 ñ 0.16 m2 BSA (mean ñ SD). Sodium diclofenac (1 mg/kg, im Voltaren 75( twice a day) was administered to patients in the Recovery Unit 48 h after surgery. Venous blood samples were collected during a period of 0-12 h and analgesia was measured by the visual analogue scale(VAS) during the same period. Plasma diclofenac levels were measured by high performance liquid chromatography. A two-compartment open model was applied to obtain the plasma decay curve and to estimate kinetic parameters. Plasma diclofenac protein binding decreased whereas free plasma diclofenac levels were increased five-fold in CPB patients. Data obtained for analgesia reported as the maximum effect (EMA were: 25 per cent VAS (CPB) vs 1O per cent VAS (control), P<0.05, median measured by the visual analogue scale where lOO per cent is equivalent to the highest level of pain. To correlate the effect versus plasma diclofen levels, the EMAX sigmoid model was applied. A prolongation of the mean residence time for maximum effect (MRTEMAX) was observed without any change in lag-time in CPB in spite of the reduced analgesia reported for these patients, during the time-dose interval. In conclusion, the extent of plasma diclofenac protein binding was influenced by CPB with clinicall relevant kinetic-dynamic consequences.