High-dose oral amoxycillin for preventing endocarditis.

High-dose oral amoxycillin for preventing endocarditis The use of oral instead of parenteral antibiotics for preventing endocarditis and the possible advantages of amoxycillin over phenoxymethylpenicillin (penicillin V) were recently discussed.' We have reported that a single 2-g oral dose of amoxycillin gave higher and more sustained serum concentrations than an equivalent dose of phenoxymethylpenicillin and that the minimum bactericidal concentrations of amoxycillin for viridans streptococci were equal to or less than 0 12 mg/1.2 A single 2-g oral dose of amoxycillin given one hour before a dental procedure, however, still fails to achieve adequate serum bactericidal concentrations for the nine-hour critical period after dental bacteraemia. We have now measured the serum amoxycillin concentrations after single oral doses of 3 g and 4 g of the drug in 13 healthy men volunteers and noted any side effects. Methods and results Amoxycillin was administered as a lemon-flavoured syrup, supplied by Bencard, dispensed as a powder and reconstituted by adding 50-65 ml water immediately before administration. Each volunteer ate a standard light breakfast one hour before taking amoxycillin and a light diet during the study. Either 3-g or 4-g doses were randomly allocated to each volunteer, and at least one week later the alternative dose was administered. Serum samples were collected from 30 minutes to 12 hours after each dose and the serum amoxycillin concentrations measured with a Sarcina lutea NCTC 8340 plate diffusion method. The table shows the amoxycillin concentrations observed after each dose. Peak concentrations occurred 1i-2 hours after administration, and the mean peak serum concentration for the 3-g and 4-g doses were 27-8 and 34-1 mg/l amoxycillin respectively. The mean serum half life for both doses was 1 hours. The mean area under the curve for the 4-g dose was 100 9 mg hour/l (SD 25 74), and that for the 3-g dose was 76-7 mg hour/I (SD 12-24). The difference between the areas under the curve was statistically significant (p < 0 01, paired student's t test). Although the 4-g dose had a higher total bioavailability than the 3-g dose, as indicated by the area under the curve, our results suggest that it was less well tolerated than the 3-g dose. After the 4-g dose four volunteers had diarrhoea, one developed "fruity burps," and another suffered from heartburn two hours after the dose. After the 3-g dose only two volunteers had diarrhoea and one developed nausea. In all volunteers, …