The bioavailabilities of cefadroxil,cefalexin, cefixime, cefprozil,and cefradine are not affected by food. Cefaclor may be givenwithout regard to food but absorption of an extended-releasepreparation may be increased by food. The bioavailabilities ofcefetamet pivoxil and cefuroxime axetil may be increased by administration with food.
Clinical evidence,mechanism, importance and management
A study in 18 healthy subjects given a single 250mg capsule of cefaclor after an overnight fast or within 30 minutes of different meals found bioavailability was not significantly affected by food. The rate of absorption and maximum plasma levels were decreased: a low-fat vegetarian diet produced smallest decrease in maximum plasma levels (26%) and a high-fat non-vegetarian diet produced largest decrease (47%) compared with levels achieved after an overnight fast. None of diets significantly affected AUC0-∞ of cefaclor. Therapeutic efficacy (measured by time levels were above MIC50) was not significantly altered.(See reference number 1) In a further study,healthy subjects were given a single 500mg dose of cefaclor as an extended-release tablet. The rate of absorption was decreased by food but compared to fasting state, maximum levels were increased; by 52 % for rice-based diets, by 33 % for low-fat-vegetarian food, by 29 % for high-fat non-vegetarian food, by 12.5 % for high-fatvegetarian food,and by 7 % for low-fat non-vegetarian food. Compared with fasting state, all diets increased time above MIC90, with a significant increase of almost 42 % with low-fat vegetarian (wheat-based) food.(See reference number 2) The manufacturers of immediate-release cefaclor capsules state that total absorption is same whether drug is given with or without food,(See reference number 3) but for extended-release preparation since absorption is enhanced by administration with food, manufacturers recommend that this preparation should be taken with meals (See reference number 4).
The manufacturers of cefadroxil state that bioavailability of cefadroxil is unaffected by food so it may be taken either with meals or on an empty stomach (See reference number 5)
A study found that bioavailability of cefetamet pivoxil was up to 25 % higher when it was given 10 minutes after a standard breakfast rather than in fasting state (See reference number 7,8). However,in another study, healthy subjects were given oral cefetamet pivoxil hydrochloride 1 g (equivalent to 693mg of cefetamet free acid) either: 1 hour before food with 200 mL of water; with a standard breakfast and a cup of tea or coffee; or 1 hour after breakfast with 200 mL of water. The cefetamet maximum plasma levels were 5.5,
5.47. and 6.57 micrograms/mL, respectively, and AUCs were 38, 35.7,and 42.8 micrograms.hour/mL,respectively, suggesting that bioavailability of cefetamet pivoxil is lowest when taken with food. The time to reach maximum plasma levels was increased from 3.3 hrs when given before food to 4.3 hrs when given with food,and 4.1 hrs when given one hour after food (See reference number 9). It was thought possible that amount of fluid taken with cefetamet may have affected absorption, but a study in which cefetamet 1 g was given under fasting conditions with either 250 or 450 mL of water found that increasing fluid intake did not affect absorption. Further, absorption when taken with food, with or without 200 mL of water was similar. It was recommended that cefetamet pivoxil should be taken within an hour of a meal to improve absorption. The delay in absorption was not considered to be of significance,especially during multiple dose therapy (See reference number 9).
A study in healthy subjects given a single 400mg dose of cefixime, either in fasting state or immediately after a standard breakfast found that time to peak serum levels was increased from about 3.8 to 4.8 hrs when cefixime was given with food,probably because of delayed gastric emptying. Serum levels,AUC and 24 hour urinary recovery were similar for fasted and fed states (See reference number 10). Cefixime may be given without regard to meals (See reference number 10,11).
In a study in healthy subjects, cefpodoxime proxetil 400mg tablets were given with 180 mL of water after an overnight fast, or either 1 hour before, with, or 2 hrs after start of a high-fat meal. Dosing 1 hour before meal was similar to dosing in fasting state. However, when cefpodoxime was taken with, or 2 hrs after meal its peak plasma levels were increased by about 45 % and 46%, respectively, when compared with peak levels achieved in fasting state. The AUC was also increased,by 40%. The rate of cefpodoxime absorption was not greatly affected by food (See reference number 12). Studies with a 200mg dose of cefpodoxime have also found that food increases extent, but not rate, of cefpodoxime absorption (See reference number 13). However, extent of food effect appears to be greater with 400mg dose. This is possibly because bioavailability of 400mg tablets is less than that of 200mg tablets, so food may have a greater effect on higher strength preparation (See reference number 12). In another study by same authors AUC and urinary excretion of cefpodoxime proxetil 200mg given as a suspension were higher (11% and 14%, respectively) when taken with a high-fat meal rather than in fasting state. Maximum plasma levels were not affected by a high-fat meal but time to achieve maximum levels was prolonged (See reference number 14).
The manufacturers state that bioavailability of cefpodoxime proxetil 100mg tablets and suspension is increased by food (See reference number 15,16). The studies(See reference number 12-14)suggest increased bioavailability of tablets, but possibly not that of suspension, when given with food may be clinically significant.
A study in healthy subjects found that, although food caused slight changes in rate of absorption of a 1-g dose of cefprozil its pharmacokinetics (including total absorption) were not significantly affected (See reference number 17).
A study in healthy subjects given cefradine 500mg in fasting state or immediately after a meal found time to peak levels was increased from 0.8 hrs to 2 hrs by food. Peak serum levels of cefradine were reduced by 45 % when it was given after food. However, half-life and AUC were not affected.(See reference number 18)The manufacturers state that cefradine may be given without regard to meals (See reference number 19).
A study in healthy subjects given cefuroxime axetil 500mg intravenously or oral doses of 125mg to 1 g with or without food found that 36 % and 52 % of a 500mg oral dose was absorbed in fasting and fed states respectively (See reference number 20). In another study in healthy subjects,a single 1-g dose of cefuroxime axetil was given 2 hrs before or 35 minutes after a standard cooked breakfast. The bioavailability of cefuroxime was markedly enhanced by food (See reference number 21). The manufacturer notes that optimum absorption of cefuroxime axetil occurs when it is given after a meal (See reference number 22). This is probably because of delayed gastric emptying and transit which allowed more complete dissolution and absorption (See reference number 21).
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