A parsimonious mathematical model of pulse modulated regulation of non-basal testosterone secretion in the male is developed. The model is of third differential order, reflecting the three most significant hormones in the regulation loop, but is yet shown to be capable of sustaining periodic solutions with one or two pulses of gonadotropin-releasing hormone (GnRH) on each period. Lack of stable periodic solutions is otherwise a main shortcoming of existing low-order hormone regulation models. Existence and stability of periodic solutions are studied. The periodic mode with two GnRH pulses on the least period has not been described in medical literature but is found to explain experimental data well.
BackgroundMotor function assessments with rating scales in relation to the pharmacokinetics of levodopa may increase the understanding of how to individualize and fine-tune treatments.ObjectivesThis study aimed to investigate the pharmacokinetic profiles of levodopa-carbidopa and the motor function following a single-dose microtablet administration in Parkinson’s disease.MethodsThis was a single-center, open-label, single-dose study in 19 patients experiencing motor fluctuations. Patients received 150% of their individual levodopa equivalent morning dose in levodopa-carbidopa microtablets. Blood samples were collected at pre-specified time points. Patients were video recorded and motor function was assessed with six UPDRS part III motor items, dyskinesia score, and the treatment response scale (TRS), rated by three blinded movement disorder specialists.ResultsAUC0–4/dose and C
max/dose for levodopa was found to be higher in Parkinson’s disease patients compared with healthy subjects from a previous study, (p = 0.0008 and p = 0.026, respectively). The mean time to maximum improvement in sum of six UPDRS items score was 78 min (±59) (n = 16), and the mean time to TRS score maximum effect was 54 min (±51) (n = 15). Mean time to onset of dyskinesia was 41 min (±38) (n = 13).ConclusionsIn the PD population, following levodopa/carbidopa microtablet administration in fasting state, the Cmax and AUC0–4/dose were found to be higher compared with results from a previous study in young, healthy subjects. A large between subject variability in response and duration of effect was observed, highlighting the importance of a continuous and individual assessment of motor function in order to optimize treatment effect.
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