摘要:

Gentamicin uptake and toxicity was studied in a nontransformed cell line obtained from the S1 segment of the proximal tubule epithelium of a transgenic mouse. Cytotoxicity was assayed using the dye 3‐(4,‐5dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT). Gentamicin uptake was assayed by a fluorescence polarization assay. No differences in toxicity were found among cells incubated for 4 hours in complete culture medium, enriched Kreb's buffer alone, or enriched Krebs' buffer with added 300 μg/mL gentamicin, 0.5 mmol/L L‐lysine, or gentamicin plus L‐lysine. Uptake of 300 μg/mL gentamicin was minimal at zero time and increased as a function of time. Uptake of gentamicin at 4 hours was positively correlated with medium gentamicin concentration. Addition of 0.5 mmol/L L‐lysine inhibited uptake of 300 μg/mL gentamicin 38.9 ± 10.2%. No other amino acid, including D‐lysine or arginine, significantly changed gentamicin uptake. The authors conclude that gentamicin and L‐lysine share a specific uptake mechanism located in the apical membrane of re

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb03905.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

This study was carried out to assess the effects on gastric acidity of placebo twice daily (bid), nizatidine 150 mg bid, nizatidine 300 mg bid, and ranitidine 300 mg bid by means of continuous 24‐hour intragastric pH monitoring. Twelve patients with duodenal ulcer in remission were randomized to receive in single‐blind fashion the above medications on four separate occasions, at least 1 week apart. The three active regimens produced higher pH values (P<.001) and maintained gastric pH above 3.0 units for a longer period (P<.001) than placebo in all time intervals but evening. Nizatidine 150 mg bid caused a lower rise in pH than nizatidine 300 mg bid (P<.01) and ranitidine 300 mg bid (P<.05) during both the daytime and the whole 24 hours. In these time windows also the time spent above 3.0 pH units was significantly shorter for the former regimen than for 300 mg bid of both nizatidine (P<.01) and ranitidine (P<.05). There was no difference between the latter two dosing schedules in terms of both potency and duration of action in all the time intervals considered. It is concluded that twice daily doses of H2blockers are more effective than placebo in reducing gastric acidity. Three hundred milligrams twice daily of both nizatidine and ranitidine produce a significantly greater and longer‐lasting acid suppression than 150 mg bid of nizatidine. Our study also confirms the greater effectiveness of H2antagonists during nighttime than during day

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb03906.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Fourteen antimitochrodrial antibody‐positive patients (13 women, 1 man) with biopsy‐proven primary biliary cirrhosis, aged 40 to 71 years (mean, 57 years) weighing 43 to 102 kg (mean, 63 kg), along with 14 age‐ and sex‐matched healthy controls, received a single 1.0‐ to 1.2‐g dose of intravenous antipyrine. Plasma antipyrine levels were determined during a 12‐ to 24‐hour period. Patients' mean serum chemistry values were: albumin, 3.9 g/dL (range, 3.1–4.4) and total bilirubin, 1.9 mg/dL (range, 0.3–10.9). Seven of the fourteen patients had cirrhosis. Mean kinetic variables for antipyrine in controls and primary biliary cirrhosis patients were: Vd, .54 versus .49 L/kg; half‐life, 12.0 versus 15.1 hours (P<.07); clearance, .55 versus .41 mL/min/kg (P<.04). Within the primary biliary cirrhosis group, there was no correlation between total bilirubin and clearance (r = .09), nor did clearance vary significantly among histologic categories. Clearance of antipyrine in primary biliary cirrhosis patients is reduced by an average of 25%, but the clinical prognosticators of serum bilirubin levels and histologic grade do not correlate with or predict the degree of

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb03907.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The authors conducted a retrospective review of 21 United States trials of ranitidine in acid peptic diseases and compared the adverse events in elderly (≥65 years) and nonelderly (<65 years) patients. Ranitidine dosages ranged from 150 mg/day to 300 mg twice daily for treatment periods of 4 to 52 weeks. Of the 4041 patients included in this review, 402 elderly and 2188 nonelderly patients received ranitidine and 245 elderly and 1206 nonelderly patients received placebo; 29%, 29%, 32%, and 26% of these patients, respectively, reported some type of adverse event. When only drug‐related adverse events (as judged by the investigators under blinded conditions) were evaluated, these percentages dropped to 2%, 2%, and 1% and 2%, respectively. Gastrointestinal adverse events (e.g., nausea and diarrhea) and central nervous system adverse events (e.g., headache and dizziness) were the most common (0.7% and 0.8%, respectively), with comparable incidence rates in the elderly and nonelderly patients. The authors conclude that ranitidine is as safe in elderly patients as it is in nonelderly patients. No difference in the incidence of adverse events was found between older and younger patients who received ranitidine or plac

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb03908.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The plasma and red blood cell pharmacokinetics and bioavailability of the natural source (RRR, d) and all racemic (all rac, dl) stereoisomers of alpha‐tocopherol were studied in 12 men in a double‐blind randomized crossover study. Subjects were administered two 400‐mg soft‐gelatin capsules of either RRR or all rac alpha‐tocopherol. Plasma alpha‐tocopherol concentrations were determined by high‐performance liquid chromatography at various time intervals for up to 96 hours postadministration. Pharmacokinetic modeling of the data showed that alpha‐tocopherol was absorbed after a 2 to 4 hour lagtime and maximum plasma concentration occurred from 12 to 14 hours postadministration. There were no significant differences in the Ka, t1/2 α, β, or t1/2 β between RRR and all rac. Mean plasma alpha‐tocopherol concentrations were greater for RRR than all rac from 10 to 96 hours postadministration and significantly greater at 24 hours (P<.05). The red blood cell alpha‐tocopherol concentration from the RRR preparation was significantly greater than from the all rac preparation from 24 to 96 hours postadministration with Cmaxfor RRR (4.8 μg/mL) significantly greater than for all rac (4.0 μg/mL, P<.05). The RRR AUC0–96for both plasma and red blood cells were significantly greater than the all rac AUC0–96(P<.05) indicating a greater bioavailability of RRR versus all rac alpha‐tocopherol. This difference in overall bioavailability was apparently not due to a si

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb03909.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Measurement of the absolute bioavailability of phenytoin (PHT) derived from test doses of Phenytoin prodrug (PPD) at therapeutic PHT serum concentrations is complicated by two problems: 1) the area under the serum concentration versus time curve (AUC) produced by a given size of test dose will vary directly with background PHT serum concentration due to the nonlinear pharmacokinetic properties of PHT; 2) PPD is more water soluble than PHT, making renal excretion of PPD more likely. The authors describe a double‐stable isotope method that obviates these two problems. Using only six subjects, the authors were able to demonstrate bioequivalence of PHT derived from intravenous PPD with intravenous PHT by current FDA standards for AUC ratio of test/reference formulation (90% confidence intervals between 0.80 and 1.20; ratio ⋝ 0.80 in ⋝ 80% of subjects; statistical power to detect a difference of 0.20 with a probability of

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb03910.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY