ISSN:0163-4356    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Summary:Aminoglycoside therapy is routinely monitored at many institutions. It is widely known that serum concentrations of gentamicin and tobramycin may differ markedly among patients receiving the same doses of these drugs. One possible source of this variability may be interlot variation in the concentration of these drugs in commercial preparations. A study was designed to evaluate inter‐ and intralot variation in gentamicin and tobramycin concentrations at the labeled concentrations of 10 and 40 mg/ml. Multiple samples from six to 10 lots of commercially available gentamicin sulfate injection (Elkins‐Sinn, Inc.) and tobramycin sulfate injection (Eli Lilly & Co.) were studied at each concentration. The actual percentage concentration of gentamicin in various lots ranged from 101 to 134% of the labeled concentrations; the actual percentage range was 101‐109% at 10 mg/ml and 102‐134% at 40 mg/ml labeled concentration. The actual percentage concentration of tobramycin in various lots ranged from 103 to 122% of labeled concentration; the actual percentage range was 107‐117% at 10 mg/ml and 103‐122% at 40 mg/ml labeled concentration. The intralot variation was <4% for both drugs at two concentrations. Based on these results, an 80‐mg dose may in fact contain 107 mg of gentamicin or 98 mg of tobramycin. This may be clinically important in the care of patients and may at least in part explain the large variation in serum concentrations and difficulty in prediction of dosage requirements from routine monitoring. Furthermore, the available literature on pharmacokinetics, efficacy, and toxicity has not considered this interlot variation in aminoglycoside concentration. Our data imply that this variation should be appreciated for optimal therapy with gentamicin and tobramycin.

ISSN:0163-4356    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Summary:The concentrations of total proteins, albumin, &agr;1‐acid glycoprotein (AGP), and nonesterified fatty acids (NEFA) were measured in the serum of 21 newborn infants and 13 children, aged 1‐13 months, and in the plasma of 31 volunteers, 25 patients with renal failure, 27 patients with cirrhosis, 39 uremic patients undergoing hemodialysis, and 20 elderly subjects. The concentration of albumin in the volunteers was higher than in all other groups. The concentration of AGP in the volunteers was higher than in newborn infants but lower than in elderly subjects, patients with renal failure, and those with chronic uremia. The concentration of NEFA in volunteers was higher than in newborn infants and patients with renal failure and lower than in elderly subjects and patients with cirrhosis.

ISSN:0163-4356    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Summary:Total platinum kinetics were studied after the administration of two formulation products of cisplatin: the lyophilized form and a ready‐to‐use solution. Twelve patients received both preparations during two successive cycles in a randomized crossover study. Platinum concentrations in plasma and urine were measured by atomic absorption spectrometry. Data were analyzed by means of a mixed‐effect analysis of variance. Areas under the concentration‐time curves up to 96 h were increased (p = 0.026) and slopes of the elimination phase were decreased (p = 0.035) during cycle 2 when compared with cycle 1. However, no difference in these two parameters was observed when comparing the two formulations. Three‐day urinary platinum excretion was not related to either the treatment cycle or the formulation used. Because of its convenience of use and reduced risk of aerosolization, the ready‐to‐use formulation seems preferable.

ISSN:0163-4356    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Summary:The effect of variations in the volume of distribution on the precision of the ability of two methods—the Chiou and the iterative—to predict the total body clearance (TBC) of theophylline was evaluated utilizing computer simulations. Pharmacokinetic data [volume of distributions (V), elimination constants (k)] measured in a group of 55 adult bronchitic patients were utilized to conduct the simulations. An averageVof 0.45 L/kg was utilized to calculate TBC with the Chiou and the iterative methods. Separate simulations were conducted utilizing initial (C1) serum concentrations of 2 and 10 &mgr;g/ml. At theC1= 2 &mgr;g/ml condition, the iterative method was statistically significantly more precise (mean squared prediction error, 379.5 vs. 508.5). There were no differences when the initial serum concentration was 10 &mgr;g/ml under the simulated conditions. At the lower initial condition (C1= 2) the mean prediction error was 62.3 and 54.9% for the Chiou and the iterative methods, respectively, and it ranged from 0 to 477%. It is recommended that caution be utilized when theophylline doses are individualized using these methods.

ISSN:0163-4356    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Summary:A method is described that utilizes any two serum concentrations obtained during a multiple dosage regimen to estimate aminoglycoside pharmacokinetics. The accuracy of this method was tested theoretically using simulated patient data. In addition, the ability of this method to estimate gentamicin pharmacokinetics and predict serum gentamicin concentrations (SGC) in individual patients was evaluated and compared with the method of Sawchuk and Zaske. Based on the theoretical and patient data evaluations, reasonably accurate pharmacokinetic parameters were derived by the present method, especially when a pair of peak and trough SGC were utilized. In addition, the prediction error of this two‐point fitting method (using pairs of peak‐trough SGC) was not significantly different from that of the Sawchuk‐Zaske method. These results indicate that the present two‐point method (when using a pair of peak‐trough SGC) provides a convenient and useful approach in individualization of aminoglycoside therapy in patients.

ISSN:0163-4356    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Summary:The pharmacokinetic parameters of half‐life, volume of distribution, and steady‐state nortriptyline plasma concentration normalized to a 100‐mg/day maintenance dose were calculated in nine smokers and 15 nonsmokers. The mean normalized total nortriptyline concentration for the smokers of 118 ± 33 ng/ml was significantly lower than the nonsmokers' mean value of 158 ± 35 ng/ml. The mean normalized free plasma concentrations for the smokers of 11.4 ± 3.5 ng/ml was not different from the nonsmokers' mean concentrations of 11.5 ± 2.6 ng/ml. The smokers had a slightly higher percentage free drug values of 10.2 ± 4.0% (p = 0.08) as contrasted to 7.4 ± 1.5% free nortriptyline for the nonsmokers. The nortriptyline half‐life figures for both the free and total drug concentrations did not differ. Multiple linear regression analysis utilizing age, smoking status, sex, liver function, and the presence or absence of enzyme‐inducing or ‐inhibiting drugs as the potential independent variables and percentage free nortriptyline or total nortriptyline concentration as the dependent variable, found that smoking status explained 21% of the variation in the percentage free nortriptyline in the patients and 26% of the variation in the total nortriptyline concentrations. These preliminary data suggest that smokers ideally should be dosed at the lower end of the nortriptyline therapeutic range, whereas nonsmokers should be dosed at the upper end to maximize the antidepressant effect and minimize adverse effects.

ISSN:0163-4356    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Summary:The hemodialysis blood clearance of chloroquine was studied in four patients with chronic renal failure undergoing chronic hemodialysis. The patients were administered chloroquine (600 mg base) orally after a light breakfast. Blood samples were then obtained from arterial blood entering and venous blood leaving the dialysis machine at 0.0, 0.5, 1.0, 2.0, 4.0, and 6.0 h, and at 24.0 and 48.0 h post dialysis. The blood flow rate varied between 200 and 275 ml/min, while the dialysate flow rate was maintained at 500 ml/min. The samples were analyzed for chloroquine by high pressure liquid chromatography, and the dialysis clearance was calculated utilizing the formula:Cld=QB[(CA‐CV)/CA]. The mean extraction ratios for chloroquine were 0.238, 0.317, 0.207, and 0.216 in the four patients during the 6‐h dialysis period. The calculated dialysis clearances were 57.2, 77.0, 56.1, and 48.3 ml/min. Chloroquine hemodialysis clearance was 14.5% of total body clearance in normal subjects and in patients with chronic renal failure not on hemodialysis.

ISSN:0163-4356    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Summary:Various factors that may influence the simultaneous concentration of total and free carbamazepine (CBZ) and carbamazepine‐10,11‐epoxide (CBZ‐E) in serum of 68 children (mean age 11.8 ± 4.5 years) with epilepsy were assessed. Separation of free and bound drug fractions was achieved by ultrafiltration, and CBZ and CBZ‐E concentrations were determined using a sensitive high pressure liquid chromatographic technique. Thirty children were on CBZ monotherapy. Both total CBZ and CBZ‐E serum concentrations correlated significantly with their respective free serum concentrations. CBZ was 81 ± 3% and CBZ‐E 63 ± 9% bound. There was no correlation between the CBZ dose and either CBZ total or free serum concentrations. A statistically significant correlation was, however, observed between CBZ dose and simultaneous CBZ‐E total and free concentrations. CBZ total and free concentrations correlated significantly with those of total CBZ‐E. A significant negative correlation was observed between age and total (r= ‐0.49, p < 0.01) and free (r= ‐0.43, p < 0.025) CBZ‐E/CBZ ratios. Concomitant drug therapy (phenytoin, phenobarbitone, and sodium valproate) significantly elevated CBZ‐E/CBZ ratios.

ISSN:0163-4356    

出版商:OVID    

年代:1986

数据来源: OVID

摘要:

Summary:Zonisamide (CI‐912) is an experimental antiepileptic drug. Since this drug is to be evaluated initially as an add‐on medication, an investigation was conducted to study its kinetics in the presence of two standard antiepileptic drugs. Patients in two groups, one on maintenance phenytoin (PHT) monotherapy and the other on maintenance carbamazepine (CBZ) monotherapy, each received a single dose of four 100‐mg capsules of zonisamide; and blood samples were obtained at periodic intervals. Plasma and red blood cell (RBC) concentrations of zonisamide were measured by high performance liquid chromatography. Plasma and RBC areas under the curve produced by single doses of zonisamide in patients receiving CBZ were significantly higher than those receiving PHT (p < 0.05). Clearance values, although not statistically significantly different, were lower for the CBZ group; and consistent with this, plasma and RBC concentrations decreased more rapidly in the PHT group. The approximate values for t1/2were 36.4 h in plasma and 54.2 h in RBC for patients treated with CBZ, and 27.1 h in plasma and 35.8 h in RBC for patients treated with PHT. The RBC/plasma ratio varied eightfold within a given curve. These findings suggest that the dosage of zonisamide in epileptic patients might need to be varied depending on the comedication.

ISSN:0163-4356    

出版商:OVID    

年代:1986

数据来源: OVID