Fenoterol metabolism in man: Sulphation versus glucuronidation

Abstract

1. Plasma levels of fenoterol (F) and its conjugate metabolites were determined in healthy female subjects and in pregnant women treated for preterm labour. Sulphate (S) and glucuronide (G) conjugates could be quantified.

2. In the healthy volunteers, AUC of both the metabolites was half that of parent compound (AUC-S/AUC-F: 0·42; 0·14–1·16) (AUC-G/AUC-F: 0·49; 0·18–0·86) during i.v. administration of the drug and was several fold that of parent drug (AUC-S/AUC-F: 116·9; 36·4–353·3. AUC-G/AUC-F: 19·9; 5·1–57·5) after p.o. administration indicating extensive presystemic elimination.

3. In the healthy subjects, the AUC ratio of G:S was 1·1 (0·5–2·6) and 0·16 (0·10–0·27) after i.v. and p.o. administration, respectively, thus indicating that sulphation is the prevailing metabolic pathway in the presystemic elimination.

4. In patients, concentration ratios were used for the analysis. During continuous i.v. treatment, C_ss-S/C_ss-F was 3·8 (2·5–4·8) and C_ss-G/C_ss-F was 1·5 (0·7–2·1). During p.o. treatment C_sstrough S/C_sstrough-F was 69·4 (32·1–145·7) and C_sstrough-G/C_sstrough-F 9·4 (5·6–13·2). C_ss-G/C_ss-S was 0·6 (0·45–0·72) during i.v. and C_sstrough-G/C_sstrough-S 0·2 (0·15–0·25) during p.o. administration.

5. Thus the results in the patients confirm that F is conjugated to S and G and that in the presystemic elimination S is the prevailing metabolic pathway.