Biomedical subjects

F Hsuan

Publications and source records attributed to F Hsuan.

5 recordsLinked to original sources

PubMed2000

A small sample confidence interval approach to assess individual bioequivalence.

The concept of interchangeable pharmaceutical products has been examined in great detail in the literature. Anderson and Hauck proposed a statistical random coefficient model to study 'switchability', and coined the phrase 'individual bioequivalence' which they defined with a probability-based inequality. Since that paper there has been considerable work and discussion. The Food and Drug Administration has recommended the introduction of individual bioequivalence (IBE) and population bioequivalence (PBE) methods in a draft guidance document. The proposal in the draft guidance includes criteria for IBE and PBE and recommends the use of non-parametric bootstrap 95 per cent upper confidence intervals for the conclusion of either IBE or PBE. However, this method requires intensive computations. We have developed an alternative confidence interval procedure to assess IBE by the FDA recommended criteria. This method utilizes Howe's approximation I to a Cornish-Fisher expansion. Our proposed method is applicable to balanced or unbalanced data in a broad class of extended cross-over designs, and can be easily programmed using readily available software.

Confidence Intervals↗

PubMed1999

A method for estimating and testing area under the curve in serial sacrifice, batch, and complete data designs.

The extent of drug availability is often measured by the area under the concentration-time curve. In animal studies, experimental constraints can limit the number of observations available on each animal. Estimation of area under the curve and its standard error are straightforward when each animal is measured at each time point. Bailer and Nedelman et al., have described techniques for estimating the area under the curve and its standard error when each animal is measured once. Yeh has described a technique for the hybrid case where animals are measured more than once, but not at all time points. We describe a method for estimating area under the curve and its standard error which is applicable to all three types of designs. We give formulas for testing treatment differences, including dose trends and dose proportionality, in area under the curve for designs containing an arbitrary number of treatments. A jackknife estimator is also described.

Analysis of Variance↗

PubMed1997

An adjusted two one-sided t-test for the assessment of bioequivalence with multiple doses.

In medical practice, it has been realized that noncompliance may have an impact on the therapeutic effect of a drug therapy, regardless of race, gender, and education of patients. Therefore, it is of interest to study the impact of noncompliance on drug absorption through in vivo testing. Efron and Feldman examined dose-response relationship when noncompliance is an issue. In this paper, we study bias and variation induced by noncompliance for pharmacokinetic parameters such as the area under the curve (AUC). We use bioequivalence testing as an example to demonstrate that a false conclusion could be drawn if one ignores the effect of noncompliance. We propose a new test for the assessment of bioequivalence in multiple doses. The proposed test appears to have a substantial improvement over the usual two one-sided tests based on a simulation study.

Area Under Curve↗

PubMed1990

Single- vs multiple-dose pharmacokinetics of clozapine in psychiatric patients.

Clozapine plasma levels were monitored in 16 patients during a series of three consecutive treatments (single dose-multiple dose-single dose). Each patient received a single 75-mg dose (3 x 25 mg) with clozapine tablets, and serial plasma samples were collected over 48 hr after the dose. At 48 hr, a multiple-dose regimen was started, consisting of an initial dose escalation period followed by dosing at a constant regimen for at least 6 days. After the last dose, serial plasma samples were again obtained over 72 hr. Drug was then withheld for at least 7 days, a final single 75-mg dose was given, and plasma sampling was repeated. A subset of the patient population (N = 7) was used to test for a food effect during the single-dose treatments. The pharmacokinetic parameters between the initial and the final single dose periods were not significantly different. Similarly, there were no differences within patients when given the dose after fasting (fed 1 hr after dose) or with a meal. In contrast, the terminal elimination rate differed between the single-dose and the multiple-dose treatments (t1/2 m3 = 7.9 hr single dose and 14.2 hr multiple dose) (P less than 0.05) and the dose-normalized area under the plasma concentration/time curves increased 27% with multiple dosing. Since a previous study in patients (Choc et al., Pharm. Res. 4:402-405, 1987) showed dose proportionality of clozapine plasma concentrations during multiple-dose regimens, the present results cannot be described by Michaelis-Menten kinetics.

Adult↗

PubMed1987

Multiple-dose pharmacokinetics of clozapine in patients.

After a 2-day buildup, patients were dosed continuously with clozapine solution at three ascending dose levels (37.5, 75, and 150 mg bid for 7 days at each dose level). Following the morning administration on the twenty-third day of dosing a drug holiday was instituted which lasted for a minimum of 48 hr. Serial plasma samples were obtained during each of the periods and during the drug holiday for the calculation of the steady-state parameters AUCSS, CSSmax, and CSSmin at each dose level as well as for the assessment of the terminal elimination rate. Mean parameter values for AUCSS, CSSmax, and CSSmin showed a linearly increasing response with the dose, well described by a straight line passing through the origin. The terminal elimination appeared to follow linear kinetics and had a mean half-life of 15.8 hr (range, 5.8-33 hr).

Adolescent↗