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The objective of this study was to compare the single-dose pharmacokinetics of multilayer-release and immediate-release methylphenidate in children with attention-deficit/hyperactivity disorder. Patients 6- to 12-years-old with a DSM-IV diagnosis of [...]

Oxybutynin is used to treat patients with urinary urgency, frequency, and urge incontinence. In this 2-way, multiple-dose, crossover study, the pharmacokinetics and pharmacodynamics of once-daily controlled-release oxybutynin were compared with [...]

Although the oral route is the preferred method for morphine administration for cancer pain, many patients will require an alternate route of administration at some point during their illness. The authors studied the steady-state pharmacokinetics of morphine after administration of a novel, controlled-release suppository (MS-CRS) and subcutaneous morphine in a randomized, double-blind, two-way crossover evaluation in 10 patients with cancer pain. When administered at a 2.5:1 analgesic ratio, MS-CRS given every 12 hours showed an equivalent extent of absorption compared with subcutaneous morphine given every 4 hours (AUC0-12, 132.5 ± 30.1 versus 123.8 ± 27.3 ng•h•mL−1, P = not significant [ NS] ). Peak morphine concentrations were lower, time of peak was later, and percent fluctuation less after MS-CRS than after subcutaneous morphine (Cmax, 14.7 ± 2.9 versus 29.9 ± 5.4 ng/mL, P = .0110; tmax, 3.33 ± 0.75 versus 2.22 ± 0.15 hours, P = .0160; fluctuation, 122 ± 71 versus 356 ± 123%, P = .00160). Relative bioavailability of MS-CRS using the 2.5:1 analgesic ratio was 105%, and bioavailability from data dose normalized without regard to route specificity in metabolism was 42%. For both routes of administration there was a significant linear relationship between morphine dose and AUC (MS-CRS, r = .8568, P = .0032; subcutaneous morphine, r = .8314, P = .0055). MS-CRS morphine provides a pharmacokinetic profile consistent with dosing every 12 hours; at steady state, the extent of absorption is comparable with that of subcutaneous morphine when administered at a 2.5:1 dose ratio. MS-CRS represents a reliable, noninvasive alternative method of morphine administration for patients unable to take oral morphine. [ABSTRACT FROM AUTHOR]

Although the pharmacokinetics of oral hydromorphone has been evaluated in healthy volunteers after small single oral doses, data are not available regarding the disposition of hydromorphone and its principal metabolite, hydromorphone-3-glucuronide (H3G), at steady-state and after large oral doses. The authors studied the pharmacokinetics of hydromorphone and H3G after oral administration of an immediate-release (IR) and controlled-release (CR) formulation of hydromorphone at a daily dose of 48 ± 11 mg (range 6-216 mg) in a randomized, double-blind, steady-state, two-way crossover evaluation in 18 patients with chronic cancer pain. Controlled-release hydromorphone demonstrated equivalent bioavailability and acceptable CR characteristics, when compared with IR hydromorphone (CR vs. IR: AUC0-12 123.10 ± 20.38 vs. 118.98 ± 20.92 ng · hr · mL−1, P = NS, Cmax 17.76 ± 3.07 vs. 19.70 ± 4.04 ng · mL−1, P = N.S., Cmin 6.04 ± 1.01 vs. 5.28 ± 1.00 ng · mL−1, P = NS, and Tmax 4.78 ± 0.78 vs. 1.47 ± 0.22 hr, P = 0.0008). A significant linear relationship existed between hydromorphone dose and hydromorphone AUC (r = 0.8315, P = 0.0001) and between hydromorphone AUC and H3G AUC (r = 0.8048, P = 0.0001) over a wide dose range. The steady-state molar ratio of H3G to hydromorphone was 27:1. The authors conclude that CR hydromorphone provides a pharmacokinetic profile consistent with 12 hourly dosing and that at steady state, oral hydromorphone is extensively metabolized to H3G, although the pharmacologic activity of this metabolite remains unknown. [ABSTRACT FROM AUTHOR]