1 The present study was designed to investigate the effect of food and of a raised intragastric pH on the bioavailability of two prodrug P-lactam, antibiotics, namely bacampicillin and cefuroxime axetil. 2 Six healthy volunteers participated in an intraindividual comparison of absorption of (a) prodrug, (b) breakfast, followed by prodrug, (c) breakfast, ranitidine and sodium bicarbonate followed by prodrug, and (d) ranitidine and sodium bicarbonate, followed by prodrug. All volunteers were dosed with both bacampicillin and cefuroxime axetil under the above regimens. The drug-free periods between trials were 7 days. 3 Blood samples were obtained before and 20, 40, 60, 90, 120, 150, 180, 210 min and 4, 5, 6, 8 and 10 h after administration. The urine was collected for a period of 10 h after dosing with the antibiotic. An estimation of the relative bioavailability of the drugs under the various regimens was made by comparing the average areas under the serum concentration time curves and also the amounts recovered in the urine.4 Both food and reduced gastric acidity decreased the bioavailability of bacampicillin (as ampicillin) and these variables had an additive lowering effect on the AUC and percentage urinary recovery. Possibly this ester becomes partially hydrolyzed prior to absorption on raising the intragastric pH. Adsorption onto food components or complexing with proteins may also play a role in the reduced bioavailability of bacampicillin in the presence of food. 5 In contrast, the absorption of the cefuroxime ester was enhanced postprandially. This may be rationalized in terms of delayed gastric emptying and gastrointestinal transit which allows more complete dissolution or prolonged residence at the most favourable site of absorption in the intestine. However, the raising of the intragastric pH by the concomittant administration of ranitidine and sodium bicarbonate, reduced the enhanced postprandial absorption. Possibly the good absorption of cefuroxime axetil requires a sufficient low gastric pH to allow the drug to dissolve in the gastric juices.
The guideline is not context-specific and serves as a universal tool to facilitate clinical decision-making based on best practice evidence. (4,11) The guideline uses a riskstratification approach with a clinical algorithm, including a combination of developmental surveillance, screening and evaluation aimed at the early identification of developmental delays. (1,2,4,10) By extension, the successful implementation of the guideline also results in the appropriate referral of children with developmental delays to intervention therapies, including physiotherapy, occupational therapy and speech therapy, as well as for psychological and educational support-to optimise their developmental outcome. (1,12-14
A total of 158 volunteers each received 21 repeated oral doses of 500 mg of cefuroxime axetil (CAE) during four comparative cross-over trials. Pharmacokinetics were studied in 8 volunteers (CAE versus ampicillin), relative bioavailability and tolerance were studied in 100 volunteers (CAE versus pivmecillinam and CAE versus pivampicillin), and tolerance alone was studied in 50 volunteers (CAE versus Study A. Eight male volunteers each received 21 repeated oral doses of 500 mg of cefuroxime as the acetoxyethyl ester during one of two dosing periods. The study was a crossover comparison with 500 mg of ampicillin in the same dosage regimen during the other period. There was an interval of 3 weeks between dosing periods.The pharmacokinetics of cefuroxime and ampiciliin were studied after doses 1 and 21 of each antibiotic. On day 1 of each dosing period, the first dose was taken after breakfast, and the second dose was taken 8 h later. Then dosing was three times daily at 0700, 1300, and 1900 after meals for 6 days in each dosing period. On day 8, the last dose was taken just after breakfast.Blood samples were taken to provide serum for antibiotic assay at the following times after dosing: 0, 30, 60, 90, 120, 150, 180, and 210 min and 4, 5, 6, 7, and 8 h. After allowing the blood to clot for 30 min, the serum was separated by centrifugation at 3,000 rpm for 5 min and stored at -18°C until assay. Four timed urine collections were made from 0 to 2, 2 to 4, 4 to 6, and 6 to 8 h after dosing. The total volume of urine in each collection was mneasured, and a sample was stored until assay to calculate urinary recovery.From each serum level-time curve, the peak serum level and the time to peak were recorded, and the area under the curve was calculated by the trapezoidal method. Serum and renal clearances were derived from dose and urinary recovery in milligrams, respectively, divided by the area up to 8 h. Clearances were probably overestimated by this method but serum profiles could not be adequately described by a compartmental model, and so areas to infinity could not be estimated.
The pharmacokinetic behavior of ceftazidime was assessed after single bolus intravenous injections of 1 g to 12 male and 12 female volunteers. The kinetic handling of the drug was essentially identical in the two sexes, exhibiting twocompartment model characteristics. However, the peripheral compartment volume of distribution of ceftazidime was smaller in the females (mean 3.95 liters, compared with 6.15 liters), and this was attributed to a smaller extracellular fluid volume. Eight volunteers in each group also received single 1-g doses of ceftazidime into the vastus lateralis and gluteus maximus muscles. The time to peak concentration was longer in the women, and it was longer after injection into the gluteus maximus in both sexes, presumably because of differences in local blood flow. The bioavailability of ceftazidime may have been slightly reduced by delays in absorption. Again, body and renal clearances were similar for both sexes when allowance was made for differences in distribution volume.Ceftazidime is a new semisynthetic cephalosporin with a broad spectrum of activity (9). It is highly active, particularly against Pseudomonas sPP., Serratia spp., and indole-positive Proteus spp., organisms which have been resistant to earlier cephalosporins. It is highly stable to ,Blactamases from gram-negative organisms and to staphylococcal penicillinases. The pharmacokinetics in healthy male volunteers have been extensively studied after both intravenous (i.v.) and intramuscular (i.m.) administration (1,8,11). The present study was designed to investigate possible differences between males and females in the handling of the drug. Since more precise kinetic data are obtained after i.v. bolus injection, the main part of the study involved comparisons between groups of 12 male and 12 female volunteers after dosing by this route. In the assessment of the handling of ceftazidime after i.m. administration, eight volunteers in each group received the drug after injection into the vastus lateralis and gluteus maximus. Ceftazidime kinetics have been shown in males to be independent of dose (1, 8), and this study was carried out at one dose, 1 g, the dose size which is likely to have the widest clinical application.MATERIALS AND METHODS Subjects and trial design. A total of 12 male and 12 female healthy volunteers participated in the study. Their mean ages were 26 years (men) and 23 years (women); mean weight's, 79 kg (men) and 58 kg (women); and mean height's, 181 cm (men) and 165 cm (women). The study was carried out in the Glaxo Institute for Clinical Pharmacology after ethical approval and written informed consent had been obtained. Volunteers underwent full physical examinations to exclude those with any abnormality; hematology, biochemistry, and urinalysis screening tests were performed.The volunteers were studied in groups of four, with an interval of 1 week between each study day. All 24 volunteers were given 1 g of ceftazidime as a bolus i.v. injection, and 8 volunteers of each sex subsequently received 1 g of c...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.