ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb03972.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Drug dosing in renal insufficiency needs to be individualized whenever possible to optimize therapeutic outcomes and to minimize toxicity. Although a number of published tables that provide dosing guidelines and nomograms exist to assist in dose modification, individualization of therapy should be based on pharmacokinetic principles whenever possible. The basis equations to estimate the pharmacokinetic parameters of clearance, volume of distribution, and half‐life for intravenous drug administration of drugs with first‐order kinetics are not difficult to understand and apply. Their use should be encouraged in patient c

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb03973.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb03974.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Efforts to speed the development and review of new drugs have increased sharply in recent years. This report, which is the third in a series on trends in drug development, examines the new drug approvals of 1990, 1991, and 1992. During the 3‐year study period, the Food and Drug Administration (FDA) approved 79 new drugs, 74 of which met the Center for the Study of Drug Development's definition of a new chemical entity (NCE). Of the 74 NCEs, 36 (49%) were considered by the FDA to represent notable therapeutic gains and were selected for “priority” review (i.e., drugs rated 1P, 1A, 1AA, and 1B), and 38 (51%) were considered to represent little or no gain and received “standard” reviews (i.e., drugs rated 1S and 1C). Investigational new drug application (IND) filing and new drug application (NDA) submission dates on all 74 drugs were obtained from responses to our manufacturer surveys as well as from FDA and public sources. The mean length of the clinical phase (IND filing to NDA submission) was 6.1 years and that of the review phase (NDA submission to approval) was 2.6 years. Of the 74 NCEs, 43 (58%) were available in foreign markets at least 1 year before U.S. approval, with a mean of 5.6 years of foreign marketing. In general, 1990 to 1992 figures are similar to those in the last half of

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb03975.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Adverse drug reactions (ADR) are uncommon causes of admission of neonates to the neonatal intensive care unit. The neonate, however, is potentially at significant risk for adverse drug reactions because of underdeveloped mechanisms and systems for handling drugs (the Gray Baby Syndrome with chloramphenicol as a classic example), the fact that infants in neonatal intensive care units are often critically ill with multiple organ system dysfunction, that they may be on multiple drugs, and that they may present with an adverse drug reaction as a result of exposure while still a fetus. There is also a history of misadventures in the neonatal intensive care unit and newborn nurseries due to exposure to antibacterial agents that produced systemic effects from percutaneous absorption. In this review, an overview of the mechanisms of adverse drug reactions will be presented, followed by a general review of the experience of adverse drug reactions in neonates and some specific examples of current adverse drug reactions and a suggested approach for the prevention and evaluation of adverse drug reactions in neonates.

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb03976.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The authors have examined the analysis of adverse event data from an efficacy dose escalation trial. Unlike the analysis of efficacy data, the assumption that when a patient experiences an adverse event at a given dose, he or she will experience the same at a greater dosage level was not applicable in the analysis of adverse event data. Because the time effect is confounded with the dose effect in a dose escalation design, any assessment of a dose‐effect relationship from such a scheme is found to be preliminary and suspect. For drugs that need to be dosed with a titration schedule, a time‐dose‐specific incidence of an adverse event provides more useful information than a dose‐specific incidence. The pace of dose titration, which was found to be important in the manifestation of an adverse event, also needs to be specified. These aspects are illustrated with data from a specially designed trial. The entire study contained a placebo arm and three arms of an active drug randomized in a parallel comparative fashion. Within each of the three active drug arms, a forced titration scheme was used to raise the dose to different levels, which distinguished the three arms. With an efficacy dose titration design, the dose‐response relationship for adverse events cannot be determined without incorporating a placebo arm and other arms with different maximum allowable doses. For drugs that need to be administered with a titration scheme, incidence of adverse events needs to be presented with the dosage, the time, and the pace of

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb03977.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The differential diagnosis of idiosyncratic adverse drug reactions (ADRs) is complex because for each adverse event there are many possible drug and nondrug causes. Recently efforts have been made to computerize causality assessment methods. A new computerized, user‐friendly diagnostic aid for Bayesian assessment of adverse drug events (MacBARDI‐Q&A) is described. This computer program performs a differential diagnosis on cutaneous reactions suspected of being drug‐induced. The authors' results indicate that development of a valid, simple and user‐friendly computerized procedure for evaluating adverse drug events is possible. The ongoing development and application of MacBARDI‐Q&A and other similar programs should improve the evaluation of putative adverse drug

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb03978.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

This study was carried out to assess the efficacy of intravenous (IV) famotidine in suppressing gastric secretion over a 48‐hour period. Twenty postoperative patients requiring a nasogastric tube received famotidine 20 mg IV every 12 hours and gastric pH was measured continuously by means of an indwelling probe. A baseline recording was performed over the first 4 hours and then the drug was infused every 12 hours (q12h) over a 15‐minute period for the subsequent 48 hours. The mean pH value achieved during each time segment under active treatment was significantly higher (P<.001) than the mean basal value. Also the density distributions of minutes spent at the various pH units confirm that famotidine is highly effective (P<.001) in raising and maintaining gastric pH above 4.0 units during most of the drug‐related period (44 hours). It can be concluded that repeated intravenous boli of famotidine 20 mg every 12 hours allow us to obtain an effective control of intragastric acidity. The antisecretory action is consistent over the total 48‐hour period examined and therefore the use of intermittent infusion of famotidine seems to be advisable, as opposed to the recommended continuous IV administration of Cimetidine and ranitidine. There is, however, a considerable intersubject variability in the antisecretory response to t

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb03979.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The urinary excretion of 5‐hydroxyindoleacetic acid (5‐HIAA), the main metabolite of serotonin, reflects the content and turnover of gastrointestinal (GI) serotonin. Employing longitudinal measurements of 5‐HIAA, the authors investigated in healthy subjects (n = 43) how manipulations of serotonin synthesis affect GI serotonin. Under conditions of serotonin‐free diets, the intersubject and intrasubject variability (coefficient of variation) for 5‐HIAA excretion averaged 33% and 14%, respectively. Dietary tryptophan restrictions to 50% of minimal daily requirements (which is equivalent to a 10‐fold reduction in baseline tryptophan intake) decreased by half the urinary excretion of 5‐HIAA, irrespective of the caloric content of diet Restoration to the regular tryptophan intake produced a rapid normalization of the 5‐HIAA excretion. Neutral amino acids are known to compete with the intestinal transport absorption mechanisms of tryptophan. Administration of neutral aminoacids (1.8 g, by mouth, three times a day, before each meal) or of carbidopa (50 mg, by mouth, three times a day for 3 days) to a normal tryptophan diet failed to alter significantly the 5‐HIAA excretion. Further, neutral aminoacids failed to enhance the reduction in 5‐HIAA produced by the low‐tryptophan diet. The failure of these treatments to reduce 5‐HIAA excretion could be due to large capacity transport and decarboxylation systems for tryptophan. Other possibilities are discussed. In summary, dietary tryptophan is essential for the maintenance of GI serotonin. Reductions or increases in dietary tryptophan are the easiest and most effective method to alter GI serotonin. Finally, interpretation of the urinary levels of 5‐HIAA should take into account not only the amount of serotonin in the diet, bu

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb03980.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Improving protein and fat absorption in patients with cystic fibrosis relates to the amount of biologically active enzyme reaching the duodenum. Microencapsulated formulations are more effective than conventional products but differ in content, ability to retard acid inactivation and the pH at which they release enzymes. Contaminants in these products contribute to hyperuricosuria.

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1994.tb03981.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY