Time of Erythema Onset after Application of Methyl Nicotinate Ointments as Response Parameter: Influence of Penetration Kinetics and Enhancing Agents

Abstract

The time of erythema onset may be used as a response parameter for quantification of the cutaneous erythema response induced by methyl nicotinate. The vehicles light mineral oil (LMO; test) and medium chain triglycerides (MCT; standard) were compared with regard to the pharmacodynamic response. Moreover, the influence of penetration enhancers on the time of erythema onset was investigated under zero order penetration kinetics. The enhancers dimethyl sulfoxide, diethylene glycol monoethyl ether and three different glycerides in different concentrations were added to MCT as a standard vehicle. All preparations were applied to the forearms of volunteers under infinite dose conditions at different thermodynamic drug activity levels (0.2–3.2% of the saturation level) and different drug concentrations (0.051–0.816%), respectively. Different penetration kinetics do not influence data of erythema onset, as these data are comparable to those obtained under finite dose conditions (first order penetration kinetics). With regard to the penetration enhancers, a significantly enhanced penetration of methyl nicotinate could be observed only for diethylene glycol monoethyl ether and dimethyl sulfoxide. However, no significant difference between light mineral oil and MCT could be found with regard to penetration enhancement. The time of erythema onset is an easy and efficient parameter for quantification of the pharmacodynamic response caused by nicotinates.

Evaluation and Determinants of Underprescription of Erythropoiesis Stimulating Agents in Pre-Dialysis Patients with Anaemia

“…The increased percentage of inadequate anaemia correction when the first dialysis was unplanned is consistent with previous studies showing that the timing of referral to a nephrologist is associated with the quality of pre-dialysis care, including anaemia [22, 23]. In France, only physicians employed on staff in hospitals and dialysis centres, mainly nephrologists, were authorized to prescribe ESA therapy, so that access to these drugs rested as much on timely referral to nephrologists as on nephrologists’ clinical practice.…”

Enhancement of bioavailability by lowering of fat content in topical formulations

“…The efficacy of a formulation is usually considered to be related to the concentration of active ingredients. For example, higher nicotinate concentrations reduce the time of onset of erythema 14,15 and glucocorticoids may be classified as strong or moderate depending on their concentration in the vehicle. In the present study we found that the efficacy also could be changed by simple modifications of the proportion of water and lipids in the formulation, i.e.…”