摘要:

The clinical correlates of methylphenidate blood levels in hyperactive children and normal adults were examined in five studies. Although occasional correlations between blood levels and neuroendocrine response were noted within subjects along the pharmacokinetic time profile of the drug, no significant associations were found between blood levels and clinical response in behavioral measures or laboratory tests of attention or activity. It is unlikely that routine methylphenidate blood level determinations will become a part of the routine clinical management of hyperactive children.

ISSN:0163-4356    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

This study was undertaken to measure the blood concentrations of bupivacaine associated with a single loading dose followed by continuous epidural infusion for the management of the pain of labor and delivery with special reference to the potential for accumulation and toxicity. Four-milliliter venous blood samples were obtained every 15 min following the loading dose until delivery. If inadequate analgesia was observed just prior to delivery, an additional dose of bupivacaine was administered. Bupivacaine concentrations were measured using a double extraction technique followed by gas chro-matographic analysis using a nitrogen-specific detector. Clearance, volume of distribution, and rate of absorption were estimated from the blood concentration time data and were 43.39 ± 11.46 L/h, 67.56 ± 17.66 L, and 8.97 ± 3.69 h-1, respectively. Peak serum bupivacaine concentrations were 0.68 ± 0.14 μg/ml and occurred 0.58 ± 0.25 h following administration of the loading dose. The duration of bupivacaine infusion was 3.42 ± 0.80 h. Serum bupivacaine concentrations at delivery or just prior to administration of a supplemental delivery dose were significantly lower than the peak concentration in all patients (p < 0.001). Fetal-to-maternal serum concentration ratios were found to be 0.44 ± 0.16 for the six patients requiring a supplemental delivery dose and 0.44 ± 0.13 for the six patients receiving bupivacaine only by infusion—The data reported here illustrate that epidural analgesia for labor and delivery achieved using a single 50-mg loading dose followed by a continuous infusion of 12.5 mg/h of bupivacaine will not result in maternal or fetal accumulation or toxicity.

ISSN:0163-4356    

出版商:OVID    

年代:1984

数据来源: OVID

ISSN:0163-4356    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

Serum theophylline clearance was estimated prior to reaching steady state in 29 asthmatic children, aged 1–14 years, using methods described by Chiou et al. and Vozeh et al. Comparison of the estimated clearance by the Vozeh method (0.094 ± 0.005 L/kg/h) did not differ significantly from that estimated by the Chiou method (0.094 ± 0.005 L/kg/h). Neither estimate of serum theophylline clearance differed significantly from the calculated clearance at steady state (0.092 ± 0.006 L/kg/h). Linear correlations between predicted and observed serum theophylline clearances were found for both the Chiou (p = 0.002, r = 0.54) and Vozeh (p = 0.02, r = 0.49) methods. Estimates of the steady-state serum theophylline concentrations by the Vozeh method (10.32 ± 0.56 mg/L) and the Chiou method (10.28 ± 0.52 mg/L) did not differ significantly from each other or from the observed steady-state serum theophylline concentration (10.54 ± 0.48 mg/L). A linear correlation between predicted and observed serum theophylline concentrations was found for both the Chiou (p = 0.02, r = 0.43) and Vozeh (p = 0.001, r = 0.57) methods. These results suggest that either method of estimating serum theophylline clearance can be used to rapidly individualize therapy in children with acute asthma.

ISSN:0163-4356    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

The diurnal fluctuations in free and total plasma levels of carbamazepine (CBZ) and carbamazepine-10, 11-epoxide (CBZ-E) and their relationship with intermittent side effects were examined in 10 epileptic patients stabilized on chronic CBZ therapy alone or in combination with phenobarbital (PB). With a t.i.d. or q.i.d. dosing schedule, total plasma levels of CBZ and CBZ-E fluctuated to a similar extent (average 34% and 29%, respectively). The diurnal changes in free levels of both compounds mirrored closely those of the total levels. Free fraction values ranged from 13 to 26% for CBZ and from 24 to 66% for CBZ-E. Owing to the lower protein binding of the metabolite, CBZ-E/CBZ ratios were higher in plasma water (0.49) than in whole plasma (0.22). A good correlation was found between both total and free CBZ levels and dose-related side effects (diplopia, nystagmus). On the other hand, no apparent relationship was found between side effects and either total or free plasma CBZ-E. The correlation with the presence of neurological signs of toxicity for the sum of CBZ ± CBZ-E levels was no better than that observed for CBZ levels alone. These data do not support the hypothesis that CBZ-E contributes significantly to the development of dose-related side effects in CBZ-treated patients.

ISSN:0163-4356    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

Steady-state serum levels of total and unbound valproic acid as well as unbound fraction in epileptic children were studied in a clinical setting. Valproic acid binding parameters were analyzed and compared within vitrofindings. Daily doses of sodium valproate ranging from 29 to 73 mg/kg/day were administered per os. Considerable variation in total and unbound concentrations and unbound fractions within and between subjects was observed. In subjects evaluated in this study, serum level of total and unbound valproic acid ranged from 279 to 1,196 μmol/L and from 37 to 410 μmol/L, respectively. The unbound fraction ranged from 10.32 to 48.39%.In vivobinding parameters obtained from clinical material were as follows: association constant,Ka= 4.984 L/mmol; total binding sites,NP= 1.451 mmol/L, wherePis the molar concentration of albumin; number of binding sites per molecule of albumin,N= 2.48. Using spiked sera, binding parameters ofKa= 8.032 L/mmol,NP= 1.262 mmol/L, andN= 1.86 were found in thein vitrostudy. The association constant obtained fromin vivoandin vitrostudies were not significantly different (p > 0.05) from each other. The unbound fraction of valproic acid was concentration dependent even within the therapeutic range. An equation for estimating unbound concentration (Cf‘) or unbound fraction (fp’) from total concentration (Ct) of valproic acid is derived. The ratio of observed unbound fraction to the estimated unbound fraction (fp/fp’) was used to evaluate the variation in valproate serum binding of that clinical sample. Nine samples from hospitalized patients whose medication and diet were closely supervised showed anfp/fp’ ratio very close to 1 (mean ± SD = 1.04 ± 0.24). It is suggested that a clinical sample showing a value offp/fp’ greater than 1.76 (mean ± 3 SD) should be evaluated for the cause of the decrease in serum binding and for the associated pharmacokinetic alterations. Therefore, in clinical monitoring of valproate, determination of both total and unbound drug levels was preferable to determination of either one alone. Furthermore, an understanding of the unbound fraction of valproic acid would significantly contribute to the effective management of epileptic patients.

ISSN:0163-4356    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

The effects that renal disease and hemodialysis have on the pharmacokinetics of amoxicillin/clavulanic acid combination were studied in a patient receiving this combination for the treatment of aNocardia asteroidesinfection. Hemodialysis increased the clearance of both substances as evidenced by lower serum concentrations during the on-dialysis day, i.e., 2.3 ± 0.8 vs. 5.9 ± 1.2 μg/ml for clavulanic acid and 8.0 ± 1.8 vs. 12.4 ± 0.9 μg/ml for amoxicillin. Clavulanic acid appeared to be influenced to a greater extent as compared to amoxicillin because of its higher extraction ratio (0.74 vs. 0.44) as well as a higher observed ratio of amoxicillin to clavulanic acid during the on-dialysis day (3.59 ± 1.27 vs. 2.28 ± 0.65; p < 0.05). Comparison of the area under the serum concentration-time curve (AUC) during the off-dialysis day with published AUC values suggested accumulation of amoxicillin/clavulanic acid. These data indicate that dosage adjustments for amoxicillin/clavulanic acid may be required in patients with chronic renal failure who are on hemodialysis. Further studies in this patient population are needed before specific dosing guidelines can be provided.

ISSN:0163-4356    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

The distribution and elimination of a new β-lactamase inhibitor, sulbactam, were characterized in patients with gangrenous or perforated appendicitis. Using a two-compartment model, the distribution volumes for the central and total body were approximately 11 and 25 L, respectively. Sulbactam is rapidly distributed and eliminated with rate constants of about 3.7 and 0.7 h-1, respectively. Mean total body clearance was 311 ml/min. In contrast to previously reported data from normal subjects, surgical patients have more rapid total body clearance and larger steady-state distribution volumes.

ISSN:0163-4356    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

A retrospective study of patients receiving tobramycin compared the accuracy of predictions of actual trough serum concentrations using two commercially available microcomputer software programs. Twelve patients met the study criteria of intravenous tobramycin treatment for more than 10 days with serum concentration monitoring within the first 5 days and after 10 days of therapy. No patients received dialysis. Twenty-five serum concentrations were compared. Predictions within 0.2 μg/ml were considered clinically “exact.” No significant differences were found by chi-square analysis for any of the four possible choices (p < 0.3). One of the programs, distributed by Dista Pharmaceuticals, offers a one-compartment model, a two-compartment model, and a two-compartment prenephrotoxic option. SIMKIN, a program marketed by Medical Engineering, Inc., uses a two-compartment model. Overall, the prediction errors were small, but occasionally were clinically significant. Further evaluation of microcomputer programs for therapeutic drug monitoring is necessary to document their impact on predicting drug efficacy and toxicity.

ISSN:0163-4356    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

The serum levels of imipramine (IMI) and its active metabolite desipramine (DMI) were monitored in 90 children with primary nocturnal enuresis. Ages ranged between 5 and 14 years. Serum concentrations were determined in 21 children at 24 h after administration of a dose of 75 mg and once when steady state had been reached, 12 h after the last dose; a good correlation was seen between the total levels (IMI ± DMI) on those two occasions (r = 0.81; p < 0.01). This serves as a basis to predict the steady-state levels of IMI ± DMI reached in an individual patient. In the remaining patients the serum levels of IMI ± DMI were determined at steady state. Dosage regimens were adjusted individually to obtain a favorable response with regard to the frequency of enuresis and to the possible occurrence of side effects. Good correlation was established between the serum concentrations of IMI ± DMI at steady state and the frequency of enuresis, with a favorable response being obtained for levels greater than 80 ng/ml. Monitoring of serum levels leads to better compliance with the regimen throughout treatment.

ISSN:0163-4356    

出版商:OVID    

年代:1984

数据来源: OVID