Why has model-informed precision dosing not yet become common clinical reality? lessons from the past and a roadmap for the future.

Patient groups prone to polypharmacy and special subpopulations are susceptible to suboptimal treatment. Refined dosing in special populations is imperative to improve therapeutic response and/or lowering the risk of toxicity. Model-informed precision dosing (MIPD) may improve treatment outcomes by achieving the optimal dose for an individual patient. There is, however, relatively little published evidence of large-scale utility and impact of MIPD, where it is often implemented as local collaborative efforts between academia and healthcare. This article highlights some successful applications of bringing MIPD to clinical care and proposes strategies for wider integration in healthcare. Considerations are brought up herein that will need addressing to see MIPD become "widespread clinical practice," among those, wider interdisciplinary collaborations and the necessity for further evidence-based efficacy and cost-benefit analysis of MIPD in healthcare. The implications of MIPD on regulatory policies and pharmaceutical development are also discussed as part of the roadmap.

A model-based meta-analysis of the effect of latanoprost chronotherapy on the circadian intraocular pressure of patients with glaucoma or ocular hypertension.

Several reports have demonstrated that the efficacy of latanoprost is influenced by the time of dosing. This model-based meta-analysis validates previous findings that evening dosing is superior to morning dosing and predicts the optimal time for dosing, based on the quantitative assessment of baseline and latanoprost-treated 24-h circadian intraocular pressure (IOP) curves. The results confirm the importance of the time of dosing as a factor that influences the extent of reduction in IOP and underline the need to take this factor into consideration in the design of glaucoma trials and therapy.

Use of local hyperthermia as prophylaxis of fibrosis and modification in penile length following radical retropubic prostatectomy.

OBJECTIVE: The aim of the study was to evaluate the effectiveness of local hyperthermia in reducing possible penile shortening following radical retropubic prostatectomy. PATIENTS AND METHODS: The study population comprised 40 patients, aged 52-74 years, submitted to radical retropubic prostatectomy. Patients were divided into two groups of 20. In Group A, patients were submitted to local hyperthermia 3 weeks after surgery, three times a week, with treatment lasting 30 min. Patients received a total of 10 applications, which reached a local temperature of 39-40 degrees C. A second cycle was repeated after 1 month. In Group B, patients were submitted only to post-operative follow-up once a month. Penile length was measured in all patients both before and 3 months after surgery in the 'stretching phase' from the pubo-penile junction to the tip of the glans. RESULTS: In Group A patients (hyperthermia treatment), no variation in penile length was observed in 16 cases (80%), while the reduction ranged from 0.5-1.5 cm in four cases (20%). In Group B, 12 patients (60%) showed a reduction in penile length ranging from 0.5-2.5 cm, while penile length remained unchanged in eight patients (40%). CONCLUSIONS: Results of this study demonstrate a mild but statistically relevant reduction in penile shortening following low-grade, externally delivered penile hyperthermia, thus confirming the efficacy of this approach in preventing penile shortening caused by post-ischaemic fibrosis.

Synthesis and local anesthetic activity of alkylaminoacyl derivatives of 3-amino-1,2-benzisothiazoles.

Two series of new alkylaminoacylamino-1,2-benzisothiazoles were synthetized and assayed for anesthetic activity. The above-mentioned compounds were prepared by reaction between the appropriate amines and 3-(haloacyl)amino-1,2-benzisothiazoles, which had been obtained by acylation of a 3-amino-1,2-benzisothiazole with the required haloacylchloride. The local anesthetic activity of the compounds, isolated as hydrochlorides, was tested for surface, infiltration and trunkular anesthesia. Several compounds proved to be active in infiltration and trunkular anesthesia, whereas no compound showed local surface anesthesia. On the basis of the results obtained the structure-activity relationships were examined.