Pharmacology

Zolpidem, used to treat patients who wake in the middle of the night and have trouble getting back to sleep, is available in many formulations—immediate release (IR), controlled release, nonbuffered sublingual, and oral mist. In 2011, it was approved as a buffered sublingual tablet (ZST) as well.

Researchers from Tufts University in Boston, Massachusetts; Henry Ford Hospital in Detroit, Michigan; Transcept Pharmaceuticals, Inc. in Port Richmond, California; and Purdue Pharma L.P. in Stamford, Connecticut, compared the pharmacokinetic profile of 3.5-mg ZST with 10-mg IR oral zolpidem in 33 healthy, nonsmoking adults. Each participant was treated with 3 dosing regimens: 3.5-mg ZST after fasting, 3.5-mg ZST after a high-fat meal, and 10-mg IR after fasting. The participants remained seated or in bed for the first 4 hours after each dose.

The ZST was absorbed faster than the IR version by patients at all observed time points. The mean plasma concentration at 15 minutes and AUC_{0-15 min} were “substantially” larger for ZST than that for IR. Although sleep-inducing effects have not been clearly linked to absorption or systemic exposure, the researchers say, it can be anticipated that ZST might be more likely than IR to promote more rapid sleep resumption.

Plasma levels were notably higher in women than those in men. The researchers note that a similar gender-dependent pharmacokinetic profile has been reported for zolpidem in other studies, but the mechanism has not been established. Moreover, at 3 to 5 hours after dosing, plasma concentrations were substantially higher with IR compared with ZST. The 5-mg dose of IR cannot be assumed to be clinically equivalent to ZST at approved dosages, the researchers caution. If 5 mg of IR is substituted, plasma zolpidem concentrations at 4 to 5 hours after dosing will be much higher, raising the possibility of potentially hazardous residual sedative effects at the time of planned awakening. Thus, the researchers advise, the dose should be lower for women.

Source
Greenblatt DJ, Harmatz JS, Roth T, et al. Clin Ther. 2013;35(5):604-611.
doi: 10.1016/j.clinthera.2013.03.007.

Zolpidem, used to treat patients who wake in the middle of the night and have trouble getting back to sleep, is available in many formulations—immediate release (IR), controlled release, nonbuffered sublingual, and oral mist. In 2011, it was approved as a buffered sublingual tablet (ZST) as well.

Researchers from Tufts University in Boston, Massachusetts; Henry Ford Hospital in Detroit, Michigan; Transcept Pharmaceuticals, Inc. in Port Richmond, California; and Purdue Pharma L.P. in Stamford, Connecticut, compared the pharmacokinetic profile of 3.5-mg ZST with 10-mg IR oral zolpidem in 33 healthy, nonsmoking adults. Each participant was treated with 3 dosing regimens: 3.5-mg ZST after fasting, 3.5-mg ZST after a high-fat meal, and 10-mg IR after fasting. The participants remained seated or in bed for the first 4 hours after each dose.

The ZST was absorbed faster than the IR version by patients at all observed time points. The mean plasma concentration at 15 minutes and AUC_{0-15 min} were “substantially” larger for ZST than that for IR. Although sleep-inducing effects have not been clearly linked to absorption or systemic exposure, the researchers say, it can be anticipated that ZST might be more likely than IR to promote more rapid sleep resumption.

Plasma levels were notably higher in women than those in men. The researchers note that a similar gender-dependent pharmacokinetic profile has been reported for zolpidem in other studies, but the mechanism has not been established. Moreover, at 3 to 5 hours after dosing, plasma concentrations were substantially higher with IR compared with ZST. The 5-mg dose of IR cannot be assumed to be clinically equivalent to ZST at approved dosages, the researchers caution. If 5 mg of IR is substituted, plasma zolpidem concentrations at 4 to 5 hours after dosing will be much higher, raising the possibility of potentially hazardous residual sedative effects at the time of planned awakening. Thus, the researchers advise, the dose should be lower for women.

Source
Greenblatt DJ, Harmatz JS, Roth T, et al. Clin Ther. 2013;35(5):604-611.
doi: 10.1016/j.clinthera.2013.03.007.

Zolpidem, used to treat patients who wake in the middle of the night and have trouble getting back to sleep, is available in many formulations—immediate release (IR), controlled release, nonbuffered sublingual, and oral mist. In 2011, it was approved as a buffered sublingual tablet (ZST) as well.

Researchers from Tufts University in Boston, Massachusetts; Henry Ford Hospital in Detroit, Michigan; Transcept Pharmaceuticals, Inc. in Port Richmond, California; and Purdue Pharma L.P. in Stamford, Connecticut, compared the pharmacokinetic profile of 3.5-mg ZST with 10-mg IR oral zolpidem in 33 healthy, nonsmoking adults. Each participant was treated with 3 dosing regimens: 3.5-mg ZST after fasting, 3.5-mg ZST after a high-fat meal, and 10-mg IR after fasting. The participants remained seated or in bed for the first 4 hours after each dose.

The ZST was absorbed faster than the IR version by patients at all observed time points. The mean plasma concentration at 15 minutes and AUC_{0-15 min} were “substantially” larger for ZST than that for IR. Although sleep-inducing effects have not been clearly linked to absorption or systemic exposure, the researchers say, it can be anticipated that ZST might be more likely than IR to promote more rapid sleep resumption.

Plasma levels were notably higher in women than those in men. The researchers note that a similar gender-dependent pharmacokinetic profile has been reported for zolpidem in other studies, but the mechanism has not been established. Moreover, at 3 to 5 hours after dosing, plasma concentrations were substantially higher with IR compared with ZST. The 5-mg dose of IR cannot be assumed to be clinically equivalent to ZST at approved dosages, the researchers caution. If 5 mg of IR is substituted, plasma zolpidem concentrations at 4 to 5 hours after dosing will be much higher, raising the possibility of potentially hazardous residual sedative effects at the time of planned awakening. Thus, the researchers advise, the dose should be lower for women.

Source
Greenblatt DJ, Harmatz JS, Roth T, et al. Clin Ther. 2013;35(5):604-611.
doi: 10.1016/j.clinthera.2013.03.007.