Patient experience and physiological response to two commercially available daily disposable myopia control contact lenses.

BACKGROUND: A range of myopia management (MM) contact lenses are becoming available to practitioners. These lenses are designed to slow myopia progression and axial elongation. This study explored the initial experience of participants wearing daily disposable MM contact lenses to investigate established factors previously associated with successful lens wear. METHODS: This was a prospective, double-masked, crossover study. Twenty participants aged 18-30 years old were assigned to wear two daily disposable MM lenses in a randomised order. Visual acuity, contrast sensitivity, and amplitude/lag of accommodation were assessed at baseline, post-insertion, and after 2 and 6 h of lens wear. Self-reported lens comfort and vision quality were recorded at the same timepoints, and at 10 h post-insertion. Pairwise comparisons were performed between the two lenses at each timepoint, as well as assessing changes throughout wear. The relationship of the measured parameters to overall lens satisfaction was also assessed. RESULTS: There were no significant differences between the two MM lenses at any timepoint for any of the participant-reported parameters, including overall satisfaction. A small difference in visual acuity was noted at 6 h post-insertion, although this is unlikely to be clinically significant. Comfort decreased throughout the day, most notably at 10 h post-insertion. A moderate positive correlation was observed between participant-reported visual quality and overall satisfaction. A similar pattern was seen for comfort and overall satisfaction. Self-reported vision quality and measured visual acuity were poorly correlated, highlighting the benefit of subjectively assessing the quality of vision with these lenses. CONCLUSIONS: The participants demonstrated comparable measures across a range of measures between the two MM lenses. Notably, half of the participants demonstrated a clear lens preference, although the preferred lens varied between individuals. Candidates for MM may benefit from trialling more than one MM lens design, to maximise initial wearing satisfaction.

Highly selective inhibition of human CYP3Aa in vitro by azamulin and evidence that inhibition is irreversible.

Azamulin [14-O-(5-(2-amino-1,3,4-triazolyl)thioacetyl)-dihydromutilin] is an azole derivative of the pleuromutilin class of antiinfectives. We tested the inhibition potency of azamulin toward 18 cytochromes P450 using human liver microsomes or microsomes from insect cells expressing single isoforms. In a competitive inhibition model, IC(50) values for CYP3A (0.03-0.24 microM) were at least 100-fold lower than all other non-CYP3A enzymes except CYP2J2 ( approximately 50-fold lower). The IC(50) value with heterologously expressed CYP3A4 was 15-fold and 13-fold less than those of CYP3A5 and CYP3A7, respectively. The reference inhibitor ketoconazole was less selective and exhibited potent inhibition (IC(50) values <10 microM) for CYP1A1, CYP1B1, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP4F2, and CYP4F12. Inhibition of CYP3A by azamulin appeared sigmoidal and well behaved with the substrates 7-benzyloxy-4-trifluoromethylcoumarin, testosterone, and midazolam. Preincubation of 4.8 microM azamulin in the presence of NADPH for 10 min inhibited approximately 95% of testosterone 6beta-hydroxylase activity compared with preincubation in the absence of NADPH. Catalytic activities of CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP2E1 were unaffected by similar experiments. Incubation of azamulin with heterologously expressed CYP3A4 yielded a type I binding spectrum with a spectral dissociation constant of 3.5 microM, whereas no interaction was found with CYP2D6. Azamulin exhibited good chemical stability when stored in acetonitrile for up to 12 days. Aqueous solubility was found to be >300 microM. Azamulin represents an important new chemical tool for use in characterizing the contribution of CYP3A to the metabolism of xenobiotics.