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Methylphenidate (MP) is used in the treatment of attention-deficit hyperactivity disorder and other disorders. MP is approximately 95% bound to plasma proteins. However, studies suggest that a small portion of the drug reaches the systemic circulation. Although the extent of MP absorption after a therapeutic dose is well studied, it is less clear how much of the drug reaches the nasal mucosa. To gain an understanding of the amount of drug in the nasal cavity, we assessed the amount of MP that reaches the nasal mucosa in guinea pigs after administration of high-dose MP. Male and female Hartley guinea pigs were dosed by intratracheal instillation with 2 mg of MP or an equivalent amount of saline on Days 0 and 1. On Days 0 and 2, 1 mL of plasma was collected via an indwelling jugular vein cannula. A single nasal instillation (0.5 mL) with 0.1% bupivacaine, 0.01% polyethylene glycol-400 (PEG), or 0.1% PEG was administered on Days 0 and 2. A minimum of 1 h after the nasal instillation, the animals were euthanized by exsanguination. The plasma and nose were collected and analyzed for MP. High-dose MP did not reach any appreciable amount of MP into the systemic circulation. However, MP was found in the nose on Day 0 at a level of 0.26 +/- 0.02 mg/kg and Day 2 at 0.28 +/- 0.02 mg/kg. PEG affected the amount of MP in the nose (P =.004). PEG of 0.01% did not affect the amount of MP in the nose, but 0.1% PEG reduced MP in the nose to 0.10 +/- 0.01 mg/kg (P =.0009). We conclude that high-dose MP is not likely to reach the systemic circulation. MP levels reached the nose in the guinea pig, and its presence may contribute to the nasal symptoms associated with MP use.Temple Avenue Historic District (Vicksburg, Mississippi)
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