ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1992.tb02663.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Cocaine abuse has become one of America's leading public health problems. Its use throughout pregnancy is associated with an increased risk of abruptio placentae, stillbirth, and preterm labor. Cocaine‐associated neonatal complications include congenital malformations, decreased fetal growth, seizures, cerebral infarction and hemorrhage, auditory system deficits, sudden infant death syndrome, cardiac arrhythmias, necrotizing enterocolitis, and behavioral changes. Children followed throughout the first year of life continue to show developmental delay. Infants and children growing up in cocaine‐abusing families are at risk for drug‐related injuries. Accidental and intentional intoxication has occurred in infants and children from the smoke of freebase cocaine. The drug has also caused intoxication in breast‐feeding infants. Adolescents experimenting with cocaine are at risk, with an apparently high frequency of seizures and loss of consciousness, as well as behavioral changes and psychosocial dysf

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1992.tb02664.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

As new antidepressants have been marketed, the issue of drug‐induced seizures has assumed new relevance. The risk of such seizures depends on at least three critical factors. Of most importance are an individual's predisposing factors that may increase the risk, followed by the amount and rate of dosage titration, and the relative epileptogenic potential of the particular dru

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1992.tb02665.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Invasive group A streptococcal infection has important diagnostic and therapeutic implications in patients with necrotizing fasciitis. We cared for a man with the full‐blown syndrome in whom many features of toxic shock syndrome were present, including profound hypotension and renal failure. The diagnostic similarities of toxic shock syndrome and the toxic shock‐like syndrome caused by group AStreptococcuscould have led to inappropriate treatment. Successful therapy in our patient included high doses initially of broad‐spectrum antibiotics, repeated operative debridement of the lower leg (the affected limb), and ultimately, reconstructive surgery consisting primarily of split‐thickness skin grafts. The reemergence of invasive streptococcal infections may relate to changes either in virulence factors of the causative streptococcus or in exotoxins elaborated by this microorganism. A causative relationship between an exotoxin produced by group AStreptococcusand the toxic shock‐like syndrome has not yet been es

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1992.tb02666.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Extracorporeal membrane oxygenation (ECMO) may affect the pharmacokinetics of certain drugs. The objectives of this study were to determine (1) the pharmacokinetics of gentamicin in neonates on ECMO and compare them to reported values for a similar patient population not on ECMO, (2) if the pharmacokinetics of gentamicin differ between venous‐venous and venous‐arterial bypass, and (3) if the pharmacokinetics of gentamicin are affected by oxygenator surface area (0.6 m2vs 0.8 m2oxygenators). The medical records of 29 term neonates who received gentamicin while on ECMO were reviewed. Data collected included gentamicin dosage, peak and trough serum concentrations determined at steady state, duration of treatment, time on ECMO, daily weights, and pertinent laboratory values. An initial dosage of gentamicin 2.5 mg/kg every 18 hours is suggested for term neonates on ECMO. Dosage adjustments should be based on gentamicin serum concentrations, and modifications may also be required after E

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1992.tb02667.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Using a dog model, a sublingual form of the free base of verapamil (SLV) was developed with the intent of avoiding stereoselective first‐pass metabolism and the necessity of intravenous administration. Intravenous verapamil (IVV) 5 mg and SLV 40 mg or 60 mg were sequentially administered to seven healthy human volunteers. Electrocardiograms and serum concentrations were obtained before and periodically from 5 to 480 minutes after each dose. The time to peak serum concentration (mean ± SD) was 77.6 ± 38.1 minutes after SLV. Bioavailability of SLV was 58.2 ± 36.9% compared to IVV. Verapamil half‐lives after IVV and SLV were 2.83 ± 0.93 and 2.28 ± 0.45 hours (NS), respectively. In one subject, the time to peak effect was delayed and overall change in PR interval was minimum. In the remaining six subjects, the maximum percentage increases in PR interval after IVV and SLV were 20.6 ± 6.4% and 14.8 ± 5.5% (p<0.05), respectively. Times to peak increase in PR interval were 28.3 ± 15.7 and 57.0 ± 17.5 minutes after IVV and SLV (p<0.05), respectively. Analysis of plots of percentage change in PR interval versus serum concentration revealed a shift to the right and therefore, lesser effect of SLV than of IVV in six subjects. All seven subjects complained of oral numbness and bitter taste. In conclusion, SLV is inferior to IVV in terms of rate and extent of absorption and pharmacologic effect in delaying atrioventricular nodal conduction. Probably SLV has little clinical utility because of its slow onset and po

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1992.tb02668.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

This study assessed the Emit Qst procainamide (PA) andN‐acetylprocainamide (NAPA) assays. Accuracy and intraday precision were evaluated by repeatedly measuring PA and NAPA concentrations in spiked serum samples using Qst and high‐performance liquid chromatography methods. Interday precision was evaluated by measuring concentrations in spiked samples over 4 weeks. Correlation between methods was assessed in patient samples, and proportional, constant, and random errors were estimated. Intraday coefficients of variation (CVs) were below 6.4% for PA and NAPA for both methods; interday CVs were below 7.8%. The proportional, constant, and random errors of the PA Qst assay in patient samples were 5.7%, −0.224 mg/L, and ± 0.574 mg/L, respectively. The same errors in the NAPA Qst assay were 17.2%, 0.229 mg/L, and ± 1.79 mg/L, respectively. The Qst assays are rapid, accurate, and precise methods for routine clinical measurement of PA and NAPA, although the proportional error in the NAPA assay should be rec

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1992.tb02669.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

The pharmacokinetics, safety, and disposition of the new antimicrobial fluoroquinolone ofloxacin were evaluated after oral administration in 14 healthy, male volunteers in a double‐blind, placebo‐controlled study. Ofloxacin was administered as 100‐, 300‐, and 600‐mg doses separated by 1 week. Plasma and urine concentrations after each administration were measured using a sensitive and specific high‐performance liquid chromatographic procedure. The distribution of ofloxacin was modeled using a two‐compartment open‐body model with first‐order absorption. Maximum plasma concentrations and area under the plasma concentration versus time curve increased in a linear, dose‐proportional manner over the range studied. At all levels, within 36 hours after administration, approximately 70% of the dose was recovered in urine as unchanged ofloxacin and only minimal amounts (<4%) as metabolites. No significant changes in the distribution or elimination of the compound were found over the 6‐fold dose range. No major laboratory toxicities or clinically significant adverse effects were noted in either the oflox

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1992.tb02670.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Clindamycin is a lincosamide antibiotic that binds primarily to α1‐acid glycoprotein (AAG), an acute‐phase serum protein. Many studies have shown that AAG concentrations increase in response to stress, including infection, myocardial infarction, and trauma. The objectives of this study were to determine the serum protein binding of various clindamycin concentrations in sera with normal and elevated AAG concentrations. Serum was obtained from 4 healthy volunteers and 12 patients with pathophysiologic conditions known to elevate serum AAG concentrations. Timing for collection was determined from the literature, corresponding with the expected peak concentration for each disease state. Samples were assayed for AAG by radial immunodiffusion and were spiked with clindamycin to achieve total concentrations of 10 μg/ml (n = 18), 4 μg/ml (n = 10), and 2 μg/ml (n = 7). Protein binding was determined by ultrafiltration and subsequent high‐performance liquid or gas chromatography. Protein binding was dependent on the serum concentrations of both AAG and clindamycin. When AAG concentrations increased from 101–150 mg/dl to 201 mg/dl or greater, mean protein binding increased from 81.2% to 92.4% (p = 0.1265) and from 61.3% to 88.6% (p<0.05) at clindamycin concentrations of 2 and 4 μg/ml, respectively. With AAG concentrations between 101 and 150 mg/dl, mean protein binding increased from 62.4% at 10 μg/ml to 81.2% at 2 μg/ml (p = 0.1514). Since AAG concentrations may increase in certain patients, the concentration of free (pharmacologically active) drug may fall below the minimum inhibitory concentration for several pathogens earlier in a d

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1992.tb02671.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

A few reports in the literature describe zidovudine (AZT) pharmacokinetics in patients undergoing hemodialysis; however, the effect of continuous ambulatory peritoneal dialysis (CAPD) on the drug's disposition has not been studied. The pharmacokinetics of AZT were evaluated in five patients, age 37–62 years, who were seronegative for the human immunodeficiency virus and were undergoing CAPD. Serial plasma, urine, and dialysate samples were collected after oral administration of AZT 200 mg. Samples were assayed using radioimmunoassay (RIA). Model‐independent analysis was used to determine total plasma clearance, apparent volume of distribution, mean residence time, and half‐life. Net peritoneal dialysis clearance was calculated to measure the effect of CAPD on AZT disposition. We found wide interpatient variability in AZT pharmacokinetics. Peak serum concentrations ranged from 0.3–47.8 μm and area under the curve from 0.5–26.1 mg × hour/L. These differences resulted in corresponding differences in clearance (range 66–3176 ml/min/1.73 m2) and volume of distribution (range 16–825 L). Interpatient variability in glucuronidation may partially account for this variability. Net peritoneal dialysis clearance of AZT was 5 ml/minute. Although the effect of peritoneal dialysis on AZT disposition was negligible, clinicians should be aware of the large differences in the way in which individual patients with renal dysfunction h

ISSN:0277-0008    

DOI:10.1002/j.1875-9114.1992.tb02672.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY