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Biomedical subjects

J L Browne

Publications and source records attributed to J L Browne.

21 records · Page 2Linked to original sources

Cost-benefit analysis of prospective pharmacokinetic dosing of nortriptyline in depressed inpatients.

A retrospective chart review was conducted on depressed inpatients to determine the economic impact of prospective pharmacokinetic dosing vs. empirical dosing of tricyclic antidepressants. The benefit/cost ratio of 2.5 indicated that the benefits of prospective dosing more than doubled the cost. The prospectively dose patients were discharged significantly earlier, i.e. 6.1 days than the empirically dosed patients and they also returned to work significantly earlier, i.e. 55.4 days than the control group.

Adult↗

Two prospective dosing methods for nortriptyline.

This study compared two prospective pharmacokinetic dosing methods to predict steady-state concentrations of nortriptyline. One method required multiple determinations of the nortriptyline plasma concentration to estimate the drug's steady-state concentration. The second method required a single nortriptyline concentration drawn at a fixed time, preferably 36 hours, following a nortriptyline test dose. The 36-hour nortriptyline plasma concentrations (NTP 36h) were substituted into the straight-line equation of Cssav = 17.2 + 3.74 (NTP 36h), where Cssav is the average steady-state concentration for a 100 mg/day dose of nortriptyline. No differences were noted between the observed steady-state nortriptyline concentration of 121 +/- 19 ng/ml, the 36-hour single-point prediction mean concentration of 121 +/- 21 ng/ml, or the multiple-point prediction mean concentration of 122 +/- 19 ng/ml. Because of the similar findings between the two methods, the clinical advantages and disadvantages of each kinetic approach are discussed to put these prospective dosing protocols into their proper perspective.

Adult↗

Chronic stress impairs oxidative metabolism and hepatic excretion of model xenobiotic substrates in the rat.

Traumatic injury to both hard and soft tissue has been associated with a decrease in the rate of hepatic drug metabolism. The mechanism(s) underlying this phenomenon have yet to be determined, but may involve substances released from damaged tissues or activation of the adrenocortical axis secondary to stress. To determine whether a generalized stress response is involved in the trauma-induced perturbations of xenobiotic metabolism, rats were exposed to atraumatic stress for a period of 21 days prior to determining the disposition of antipyrine (an in vivo marker for the hepatic mixed-function oxidase system) and indocyanine green (a tricarbocyanine dye often used as an in vivo marker of active hepatic uptake). Exposure to stress resulted in a significant decrease in the systemic clearance of antipyrine, suggesting a stress-induced inhibition of hepatic oxidation. In addition, the stressed animals evidenced a decreased rate of uptake of indocyanine green by the liver, an apparent decrease in the storage of the dye within the liver, and a decreased hepatic clearance of indocyanine green (presumably due to a decrease in the KM for biliary transport). These observations suggest that atraumatic stress affects several processes involved in the hepatobiliary disposition of xenobiotics.

Animals↗