摘要:

A randomised study was conducted in healthy male volunteers to assess the pharmacokinetics of valproate after multiple 500mg (every 8 hours) or 250mg (every 6 hours) doses commencing 1 to 3 hours following an intravenous 1000mg loading dose administered over 10 minutes. Multiple blood samples were collected throughout the 73- to 75-hour study period and plasma valproate concentrations were quantified using a gas chromatographic technique. All 3 regimens produced near steady-state trough plasma concentrations generally above 50 mg/L throughout the first study day. By the morning of day 2, pseudo-steady-state conditions had been established. Overall, an intravenous 1000mg loading dose of valproic acid followed within 3 hours by oral regimens of divalproex sodium 500mg every 8 hours or 250mg every 6 hours appears to be an acceptable approach to rapidly achieve therapeutic concentrations with steady-state trough plasma concentrations above 50 mg/L.

ISSN:0114-2402    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

The pharmacokinetics of carbamazepine (CBZ) were studied in 7 patients with duodenal ulcer both before and after 14 days' treatment with omeprazole (20 mg/day), as this substituted benzimidazole has been shown to alter the pharmacokinetics of some drugs. CBZ serum levels were determined by high pressure liquid chromatography following oral administration of CBZ 400mg. Omeprazole treatment caused increases in CBZ blood levels and significantly prolonged the elimination half-life from 17.2 ± 5.9 hours to 37.3 ± 22.8 hours. Simultaneously, there was an increase in the area under the curve (AUC0-∞) from 382.3 ± 81.1 μg/ml · h to 668.8 ± 241.6 μg/ml · h, while the CBZ clearance was decreased significantly from 20.7 ± 3.4 ml/h/kg to 12.5 ± 3.5 ml/h/kg. Other parameters such as maximum plasma drug concentration (Cmax), time to reach maximum concentration (tmax), and apparent volume of distribution at steady-state (Vss) were, however, not altered by omeprazole treatment. The reduction in clearance and increase in half-life and AUC0-∞values may be attributed to inhibition of CBZ oxidative metabolism by omeprazole.

ISSN:0114-2402    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

The effects of a single dose regimen of lisinopril (10mg daily) and quinapril (10mg daily) were studied in 47 patients with mild to moderate essential hypertension. After discontinuation of previous antihypertensive treatment and a 2-week washout period, all patients received placebo for the next 2 weeks. Patients were then randomly assigned, in a double-blind fashion, to one of two groups: the first group (group L) was made up of 24 patients who received lisinopril 10mg once daily; the second group (group Q) was made up of 23 patients who received quinapril 10mg once daily. The duration of treatment was 12 weeks. Systolic (SBP) and diastolic blood (DBP) pressure and heart rate (HR) were measured every 2 weeks. Routine blood and urine investigations were performed at weeks 0, 8 and 12. Two weeks after initiation of treatment, a statistically significant reduction in both SBP and DBP was observed in both groups. Comparison between the 2 groups showed a significant reduction in SBP (p < 0.05) at week 4 and in DBP (p < 0.05) at week 8, in favour of the quinapril group (group Q). In group L, heart rate remained unchanged, while in group Q a significant reduction was observed from week 8 until the end of the study (p < 0.001). At week 12, a significant increase in serum potassium was observed in both groups compared with baseline levels (p < 0.01), without significant differences between the 2 groups. The other parameters did not show any significant change during the study. In conclusion, both drugs exhibit adequate antihypertensive effect, but quinapril seems to cause a greater fall in blood pressure and HR 4 weeks after initiation of treatment.

ISSN:0114-2402    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

The formation of the reduced metabolite of haloperidol - reduced haloperidol (RH) - was evaluated after intramuscular haloperidol injection in 13 chronic schizophrenic patients. After an overnight fast, each patient received a 5mg dose. Plasma samples were obtained prior to injection and 0.25, 0.5, 1.0, 1.5, 2, 2.5, 3, 6, 9, 12, 24, 36, 48, 72 and 96 hours postinjection. Plasma haloperidol, RH and homovanillic acid (HVA) levels were assayed by high performance liquid chromatography with electrochemical detection. Plasma haloperidol concentrations were detectable in each patient at 96 hours postinjection. The mean time to maximum (tmax) plasma concentrations was 0.86 hours. A wide interpatient variability was observed in the pharmacokinetic parameters for the population. RH was detected in only 6 patients. The mean tmaxof RH occurred at 1.37 hours. Although statistically not significant, the mean volume of distribution of haloperidol patients with RH was slightly larger compared with patients with only haloperidol (32.89vs28.33 L/kg). The mean elimination half-life of haloperidol was longer but also not statistically significant in the RH/haloperidol patients compared with haloperidol only patients (43.03vs34.37 hours). Intramuscular haloperidol injection produced a characteristic decrease in plasma HVA levels with a tmaxat 0.75 hours. Plasma HVA levels remained decreased and returned to baseline values 12 hours later. Plasma HVA levels were slightly lower in RH/haloperidol patients compared with haloperidol only patients.

ISSN:0114-2402    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

The short term pharmacokinetics of the bisphosphonate clodronate were studied in 20 patients with tumour-mediated bone disease and a wide range of renal function (creatinine clearance 13 to 112 ml/min; mean 54.8 ml/min). Clodronate 300mg was given as a single intravenous infusion over 2 hours and the concentration of drug in serum and urine was measured at intervals for 24 hours after the start of the infusion. The total clearance was 86.6 ± 7.4 ml/min (mean ± SEM), with an apparent renal clearance of 41.0 ± 4.3 ml/min, and thus a nonrenal clearance of 45.6 ± 5.2 ml/min. The range of nonrenal clearance was as great as that of renal function. Both renal and total clearance showed a significant positive correlation with renal function, as judged by endogenous creatinine clearance (r = 0.66, p = 0.002 and r = 0.62, p = 0.004, respectively). The slope of the regression line of renal clearance on creatinine clearance was 0.46, but renal clearance of clodronate exceeded creatinine clearance in 7 patients, 6 of whom had marked renal impairment. Neither nonrenal clearance nor half-life correlated significantly with renal function.We conclude that there is no need to adjust the dose interval of clodronate in patients with renal impairment, but that the dose of clodronate should be reduced in the presence of markedly impaired renal function. However, the range of nonrenal clearance is high, so that difficulties arise in dose adjustments made on the basis of renal function alone.

ISSN:0114-2402    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

The manifestation of rhinitic symptoms in 9 patients with grass pollen-induced rhinitis was studied during long term allergen exposure at physiological concentrations in the ‘Vienna Challenge Chamber’. Patients were pretreated with a single dose of azelastine (either 2.2mg orally or 0.28mg intranasally) or placebo. Nasal resistance was estimated by active anterior rhinomanometry every 15 minutes. Analysis of changes in nasal airways resistance demonstrated significant protection against allergen-induced nasal obstruction (p < 0.01) for azelastine administered by either route. The onset of action of treatment in relation to nasal obstruction was significantly more rapid for the nasal spray (135 minutes) than for the tablet (205 minutes) [p < 0.01] formulation. Similarly, the onset of effect derived from subjective assessment of symptom severity was markedly more rapid (60 minutes) after intranasal azelastine than after administration of the oral form (120 minutes). Tolerability of azelastine was good, with no side effects reported with either oral or intranasal therapy.

ISSN:0114-2402    

出版商:ADIS    

年代:1994

数据来源: ADIS

摘要:

The steady-state pharmacokinetics of tiopronin (2-mercaptopropionylglycine, 2-MPG), were studied in healthy volunteers after single (n = 10) and multiple (n = 7) oral doses. Similarly, 5 patients with cystinuria on maintenance doses of tiopronin were studied. The pharmacokinetics of tiopronin in the healthy volunteers did not differ significantly during 10 days of treatment, i.e. the area under the concentration-time curve, time to reach maximum plasma concentration, apparent oral clearance (CL/F), renal clearance (CLR), terminal elimination half-life (t½), and amount of dose excreted in urine were similar. The apparent volume of distribution (Vd/F) was, however, different and might have been due to altered plasma and tissue binding after multiple doses. The pharmacokinetics of tiopronin after multiple oral doses in healthy volunteers compared with maintenance doses in patients with cystinuria were generally the same. The terminal t½of total tiopronin was somewhat longer owing to firm protein and tissue binding. The decreased CL/F and CLRfound in the patients with cystinuria were probably a consequence of decreased glomerular filtration rate (51Cr-EDTA clearance) in this group. No differences in the pharmacokinetics of the metabolite 2-mercaptopropionic acid (2-MPA) were found between the 2 groups. The effects of tiopronin on cystine excretion in patients with cystinuria were confined to the first 12 hours after administration.We conclude that the pharmacokinetics of tiopronin were similar after single and multiple doses in healthy volunteers. At steady-state no major differences in the pharmacokinetics of tiopronin and 2-MPA were found between healthy volunteers after 10 days of treatment and patients with cystinuria on maintenance doses. The rapid decrease in cystine excretion after a single dose of tiopronin and the fast elimination of the active form (non-protein-bound) of the drug implies that the drug should be administered more often than the long terminal t½of total tiopronin suggests, because it does not seem to accumulate in the body. Thus, we propose that tiopronin should be given in divided doses, at least twice daily, for optimal efficacy in the treatment of cystinuria.

ISSN:0114-2402    

出版商:ADIS    

年代:1994

数据来源: ADIS

ISSN:0114-2402    

出版商:ADIS    

年代:1994

数据来源: ADIS