To standardize CYP2D6 allele nomenclature, and to conform with international human gene nomenclature guidelines, an alternative to the current arbitrary system is described. Based on recommendations for human genome nomenclature, we propose that alleles be designated by CYP2D6 followed by an asterisk and a combination of roman letters and arabic numerals distinct for each allele with the number specifying the key mutation and, where appropriate, a letter specifying additional mutations. Criteria for classification as a separate allele and protein nomenclature are also presented.

The CYP2D6 protein is a polymorphic isoenzyme involved in the biotransformation of several drugs including the probe drug dextromethorphan. The rise in the protein concentration, immunochemically determined with a specific antibody, was shown to occur within the first week following birth, whatever the gestational age at birth.In fetuses, the concentration of hepatic CYP2D6 protein was very low or undetectable in 70% of samples tested. In the remaining 30%, its concentration was comparable to that of newborns aged 1–7 days. This early rise was associated with spontaneous abortion in 70% of positive samples, whereas in fetuses with an intermediate CYP2D6 protein concentration, 80% were from induced abortions.The rise in CYP2D6 protein was associated with the developmental onset of dextromethorphan O‐demethylation, but not N‐demethylation, even if activity was lower in fetal than in neonatal and in adult liver microsomes.Lastly, the CYP2D6 RNA is detectable earlier than the protein and exhibits a peak of hepatic accumulation in newborns, before declining in adulthood. A positive correlation between RNA accumulation and protein concentration can be demonstrated only in the adult. This suggests that regulation is primarily at the transcriptional level, but cannot rule out the participation of post‐transcriptional events in the regulation process throughout ontogenesis.

Objective To determine the safety of ciprofloxacin in paediatric patients in relation to arthropathy, any other adverse events (AEs) and drug interactions. Methods A systematic search of MEDLINE, EMBASE, CINAHL, CENTRAL and bibliographies of relevant articles was carried out for all published articles, regardless of design, that involved the use of ciprofloxacin in any paediatric age group ≤17 years. Only articles that reported on safety were included. Results 105 articles met the inclusion criteria and involved 16 184 paediatric patients. There were 1065 reported AEs (risk 7%, 95% CI 3.2% to 14.0%). The most frequent AEs were musculoskeletal AEs, abnormal liver function tests, nausea, changes in white blood cell counts and vomiting. There were six drug interactions (with aminophylline (4) and methotrexate (2)). The only drug related death occurred in a neonate who had an anaphylactic reaction. 258 musculoskeletal events occurred in 232 paediatric patients (risk 1.6%, 95% CI 0.9% to 2.6%). Arthralgia accounted for 50% of these. The age of occurrence of arthropathy ranged from 7 months to 17 years (median 10 years). All cases of arthropathy resolved or improved with management. One prospective controlled study estimated the risk of arthropathy as 9.3 (OR 95% CI 1.2 to 195). Pooled safety data of controlled trials in this review estimated the risk of arthropathy as 1.57 (OR 95% CI 1.26 to 1.97). Conclusion Musculoskeletal AEs occur due to ciprofloxacin use. However, these musculoskeletal events are reversible with management. It is recommended that further prospective controlled studies should be carried out to evaluate the safety of ciprofloxacin, with particular focus on the risk of arthropathy.