A retrospective cross-sectional study to determine chirality status of registered medicines in Tanzania

Abstract

Medicines with a stereogenic center (asymmetric carbon) are mainly present as racemates with a mixture of equal amounts of enantiomers. One enantiomer may be active while the other inactive, alternatively one may produce side-effects and even toxicity. However, there is lack of information on the chirality status (either racemates, single active enantiomer or achiral) of medicines circulated on the market particularly in African countries. We established the chirality status of registered medicines in Tanzania by conducting a retrospective cross-sectional study. Registration data for the past 15 years from 2003 to 2018 were extracted from TMDA-IMIS database to Microsoft excel for review and analysis. A total of 3,573 human medicines had valid registration. Out of which 2,150 (60%) were chiral and 1,423 (40%) achiral. Out of the chiral medicines, 1,591 (74%) and 559 (26%) were racemates and single active enantiomers, respectively. The proportion of racemates within chiral medicines was considerably higher than single enantiomer medicines. The use of racemates may cause harm to the public and may contribute to antimicrobial resistance due to potential existence of inactive and toxic enantiomers. In order to protect public health, regulatory bodies need to strengthen control of chiral medicines by conducting analysis of enantiomeric impurity.

Figure 1

Examples of structures of (R)- enantiomers: A—D and (S)- enantiomers: A—D of chiral medicines and their activities.

Figure 2

Percentage of Level 1 ATC classification of chiral medicines; racemates is high in all groups except nervous system (N) and various (V). The codes and ATC description are as indicated in the 1st and 2nd column of Table 2.

Figure 3

Percentage of chiral medicines in level 2 ATC classification. Key: AB—Antibacterials for systemic use, AM—Anti-mycobacterials for systemic use, AC—Antimycotics for systemic use, AV—Antivirals for systemic use.

Figure 4

Number of racemate and single enantiomer medicines in each pharmacological group in level 2 ATC classification. Key: AB—Antibacterials for systemic use, AM—Anti-mycobacterials for systemic use, AC—Antimycotics for systemic use, AV—Antivirals for systemic use.

Figure 5

Pharmacological groups of medicines listed in NEMLIT. The codes and ATC description are as indicated in 1st and 2nd column of Table 2.