Exploring the Impact of Renal Impairment on PD 0200390 Pharmacokinetics: Insights into a Promising Insomnia Treatment

The study focuses on PD 0200390, a ligand for the alpha-2-delta protein, which is being explored as a novel treatment for insomnia. It has been shown to increase slow-wave sleep in rats and is deemed safe and well tolerated in human trials, with the primary elimination route being renal excretion. The research aims to understand the impact of renal impairment on the pharmacokinetics and tolerability of a single dose of PD 0200390, to ascertain if dosage adjustments are necessary for those with renal dysfunction.

In an open-label trial, 26 subjects were divided into groups based on their renal function: no impairment, mild, moderate, and severe. They received a single oral dose of 25mg PD 0200390. The study found that the drug was well absorbed and reached peak plasma concentration within 1.66 to 3.24 hours. The half-life of PD 0200390 was 5.36 hours in subjects with normal renal function, which increased with the severity of renal impairment. The oral and renal clearance rates were found to decrease with worsening renal function, while the area under the curve (AUC) values increased by 56%, 117%, and 436% in subjects with mild, moderate, and severe renal impairment, respectively, indicating a higher exposure to the drug.

Regression analysis confirmed a strong correlation between oral and renal clearance rates and estimated creatinine clearance (CLcr). The drug was well tolerated in subjects with mild to no renal impairment, but those with severe renal impairment experienced a higher frequency of adverse events. The most common side effects were somnolence, dizziness, and headache, which were most intense in the severe renal impairment group.

The study concludes that the pharmacokinetic parameters of PD 0200390, including oral and renal clearance rates and AUC, are predictably affected by the degree of renal function. This suggests that dosage adjustments may be necessary for patients with renal impairment to account for increased drug exposure.