ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb01919.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

This series of two articles on postmarketing safety surveillance has been developed for use in training clinical pharmacologists. It provides a basic overview useful to clinical pharmacologists in a range of occupational functions. These reports can be used as the basis for a lecture or as background reading material for establishing a unit on postmarketing surveillance. For teaching rounds, multiple illustrations and summary tables have been included. These can readily be made into 35‐mm slides or transparencies. Table I outlines the curriculum on postmarketing surveillance for the clinical pharmacologist. The first article describes postmarketing surveillance within the continuum of the drug approval process. The relationship of clinical trials to safety surveillance after drug approval are reviewed. The importance of spontaneous adverse drug experience reporting also is discussed. The second article focuses on the regulatory aspects of postmarketing surveillance and discusses the FDA's (Food and Drug Administration) Spontaneous Reporting System. The two types of adverse experience reports in the Spontaneous Reporting System are described: reports voluntarily submitted by health care providers and others, and reports manufacturers are required by regulation to submit. The clinical pharmacologist's role in postmarketing surveillance is define

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb01920.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The steady‐state pharmacokinetics of didanosine (DDI) and ketoconazole (KET) were evaluated when the agents were administered alone or concurrently to patients seropositive for the human immunodeficiency virus. Using a randomized, three‐way crossover design, multiple oral doses of DDI (375 mg twice daily for 4 days), KET (200 mg daily for 4 days) or the combination were administered under fasting conditions. When DDI and KET were coadministered, KET was given 2 hours before the morning dose of didanosine. Serial blood samples and total urine output were a collected after the administration of a final single dose on day 5 of each treatment session. Samples were analyzed using high‐pressure liquid chromatography (HPLC)/ultraviolet (UV) or fluorescence methods specific for unchanged DDI (plasma and urine) or KET (plasma only). Pharmacokinetic parameters were calculated using noncompartmental methods. The average DDI maximum peak plasma concentration (Cmax) value at steady state was significantly less when DDI was administered with KET (1836 ng/mh) than when DDI was administered alone (2094 ng/mL), although the magnitude of the decrease was only 12%. Didanosine area under the curve (AUC(0 — τ))for the combination (2872 hr.ng/mL) was 8% less than when DDI was given alone (3107 hr.ng/mL); the difference was not significant. There were no significant differences among the other evaluated parameters (time to reach peak concentration [tmax], half‐life [t1/2], renal clearance [CLR], or urinary recovery [UR]) between the two DDI treatments. There were no significant differences among any of the pharmacokinetic parameters between the two KET treatments. It is concluded that the pharmacokinetics of DDI and KET are not affected to a clinically significant degree by coadministration of multiple oral doses of the two agents under the current study conditions. It is not necessary to alter the dosing regimen of either drug so long as KET is administered 2 hours

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb01921.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Limited data have been published that compare the pharmacokinetic parameters of vancomycin in elderly versus young patients. This study was designed to assess vancomycin pharmacokinetics in 148 elderly (≥60 years of age) and 140 young (18–59 years of age) hospitalized infected patients. Serum vancomycin concentrations were determined using fluorescence polarization immunoassay. Serum concentration‐versus‐time data were fitted to a two‐compartment Bayesian forecasting program. Elderly versus young vancomycin pharmacokinetic parameters derived were as follows (patients with serum creatinine ≤.1.5 mg/dL): mean ± standard deviation terminal disposition half‐life (t1/2) of 17.8 ± 11.8 versus 7.5 ± 6.7 hours, respectively, P<.05; volume of distribution (Vz) of 74.2 ± 32.3 versus 67.0 ± 30.7 L, respectively, P = .16; and total body clearance (CL) of 0.71 ± 0.41 versus 1.22 ± 0.50 mL/min/kg, respectively, P<.05. Comparing subjects with normal serum creatinine values (≤1.5 mg/dL), the elderly required smaller daily doses as compared with the young group to maintain target peak and trough vancomycin serum concentrations (18.2 ± 5.8 versus 25.2 ± 7.8 mg/kg/day, P<.05). Stepwise multiple regression models for the pharmacokinetic parameters were developed to assess the predictive power of age, controlling for the effects of gender, total body weight, serum creatinine, and creatinine clearance. Age was consistently an independent and significant predictor of t1/2, Vz, and CL. These data demonstrate that elderly patients exhibit significant differences in vancomycin pharmacokinetic parameters compared with young patients and constitute a patient population in need of individualized vancomycin dosing due to substantial heterogeneity in physiologic and ph

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb01922.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

In vitro activity of new dual‐acting antibacterial Ro 23–9429 was tested against 1294 bacterial isolates from patients in a major tertiary care referral hospital in Saudi Arabia. Its activity was compared with that of ciprofloxacin, fleroxacin, ampicillin, cephalothin, cefoxitin, cefotaxime, ceftazidime, piperacillin, oxacillin, gentamicin, amikacin, imipenem, and vancomycin. Of the 621 members of Enterobacteriaceae tested, every single isolate was inhibited by Ro 23–9429 at minimum inhibitory concentration ranging between<.03 and 8 μg/mL. No other antimicrobial tested was as active as this dual‐acting cephalosporin‐fluoroqinolone. Similarly, all of the 255 isolates of Acinotobacter, Aeromonas hydrophila, Pseudomonas aeruginosa, and Xanthomonas maltophilia were susceptible to Ro 23–9429. It inhibited all the 120 isolates of methicillin‐resistant Staphylococcus aureus. Its in vitro activity against coagulase‐negative staphylococci and enterococci was superior or comparable to that of other drugs that are commonly used in c

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb01923.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The pharmacokinetics of the H1‐receptor antagonist cetirizine were studied from 0 to 72 hours after a single dose of 20 mg in 5 patients with chronic hepatocellular liver disease (group A), in 5 patients with chronic cholestatic liver disease (group B), and in 16 healthy volunteers. The renal function of patients and volunteers was normal (creatinine clearance ≥ 70 mh/min). Cetirizine pharmacokinetics were similar in the two groups of patients. The elimination t1/2 was prolonged in patients (mean ± standard deviation; group A: 14.32 ± 2.30 hours; group B: 13.86 ± 3.14 hours) in comparison with the values observed in volunteers (9.42 ± 2.4 hours). A reduced apparent oral body clearance also was observed in patients (group A: .48 ± .23 mL/min/kg; group B: .41 ± .09 mL/min/kg) in comparison with volunteers (.74 ± .19 mL/min/kg). No differences were observed in the mean cumulative urinary excretion between patients (group A: 69 ± 15%; group B: 69 ± 13%) and volunteers (

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb01924.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The protein binding of FCE 22,178 in humans was determined ex vivo by equilibrium dialysis using plasma samples obtained from a dose‐ranging study in normal male volunteers. These data suggested that FCE 22,178 may exhibit concentration‐dependent protein binding over an in vivo concentration range of .8 to 64 μg/mL. Increase in free fraction at higher plasma drug concentrations corresponded directly to the dose‐dependent increase in renal drug clearance. Nonlinear parameter estimation showed that FCE 22,178 binds tightly to plasma proteins with an apparent equilibrium association constant of 1.44 × 105mol/L. Predicted change in the free fraction is consistent with the observed changes in renal cl

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb01925.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Pursuant to anecdotal case reports of a possible drug‐drug interaction between cyclosporine and diclofenac, an open, two‐period crossover study in 24 healthy male volunteers was undertaken in which a single oral dose of 300 mg cyclosporine was administered alone and on day 8 of multiple oral dosing of 50 mg diclofenac every 8 hours. Serial blood samples were obtained over 48 hours after each cyclosporine dose and over a dosing interval for diclofenac on day 7 (diclofenac alone) and day 8 (coadministration of diclofenac with cyclosporine). The mean pharmacokinetic characteristics of cyclosporine were unchanged during coadministration with diclofenac. Based on area under the curve comparison, lack of a pharmacokinetic interaction was conclusively demonstrated for the extent of cyclosporine absorption. The diclofenac maximum plasma concentration and area under the curve over a dosing interval were significantly increased during coadministration; however, a straightforward interpretation of the statistical results was confounded by pronounced variability in diclofenac pharmacokinetics. The results underscore the need for continued caution when cyclosporine and diclofenac are coadministe

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb01926.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The acute analgesic activity of an Histamine antagonist, terfenadine 60 mg, and an H2‐histamine antagonist, ranitidine 150 mg, were compared with ibuprofen 600 mg and placebo in a double‐Mind, placebo‐control Jed, parallel‐group study. Treatments were administered to a total of 127 patients 1 hour before oral surgery. Analgesia was assessed every 30 minutes for 240 minutes after surgery. Analgesic efficacy was compared using the following standard pain intensity scales: visual analog scale, category, graphic rating, and global evaluation. Ibuprofen was significantly better than all other treatments for all measures of analgesic activity. The effects of terfenadine and ranitidine were similar to placebo. These data indicate that pretreatments with a single dose of a histamine receptor antagonist specific for either the H1‐ or H2‐receptor does not produce analgesia in an oral surgery model of acute pain with overall assay sensitivity, suggesting that antihistamines that act primarily at peripheral sites are devoid of analgesic activity. These data contrast with other studies that have demonstrated analgesia using centrally acting antihistamines such as hydroxyzine, phenyltoloxamine, or o

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb01927.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The new H1‐receptor antagonist, cetirizine, is eliminated primarily unchanged by renal excretion and is thus potentially useful for relief of pruritus in patients with hepatic dysfunction, in whom many H1‐receptor antagonists are contraindicated. The authors studied the elimination of cetirizine in six patients with primary biliary cirrhosis. In contrast to data obtained in healthy adults with normal hepatic function reported in the medical literature, they found that the mean serum elimination half‐life value of cetirizine, 13.8 ± 1.8 hours, was longer, and the mean clearance rate, 0.44 ± 0.10 mL/min/kg, was lower (P<.05). The mean peak serum cetirizine concentration, 498 ± 118 ng/mL, was higher, the mean area under the curve, 6438 ± 1621 ng/mL/hr, was larger, and the mean fraction of the dose excreted as unchanged cetirizine in the urine, .32 ± .14, was lower (P<.05). The duration of action of cetirizine was prolonged, as evidenced by significant suppression of the histamine‐induced wheal and flare for 48 and 72 hours, respectively, after a single dose. Cetirizine elimination was impaired in patients with hepatic

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb01928.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY