Understanding the Role of Willingness to Cannibalize in New Service Development

The objective of the present study is to develop a model of explaining new service development behavior using the concept of willingness to cannibalize existing sales, current capabilities and prior investments. The paper is structured as follows. First, we review the literature relevant for our work. Second, we explain our conceptual model. Next, we report on the research method used and present empirical evidence from 217 service firms. We close with a discussion and recommendations for future research.

Population pharmacokinetics of the novel anticancer agent KRN7000

Purpose: KRN7000 is a novel anticancer agent, acting through stimulation of the immune system. The first clinical trial with this agent, which included pharmacokinetic studies, has recently been completed. The aim of the study presented here was to develop a population pharmacokinetic model for KRN7000. Methods: Plasma concentration-time data were gathered from 24 patients enrolled in a phase I trial in which KRN7000 was administered as a weekly slow injection at doses ranging from 50 to 4800 μg/m2. These data were used to build a pharmacokinetic model using the nonlinear mixed-effect modeling (NONMEM) program. The model was validated by performance of 200 bootstraps. Results: A three-compartment model with inter-individual variability on the central and two peripheral volumes of distribution (V1, V2 and V3) and on clearance (CL) adequately described the data. The final estimates were: V1 2.34 l, V2 2.61 l, V3 2.13 l, and CL 0.130 l/h. Of 24 covariates tested, including both demographic and pathophysiological factors, none showed a significant relationship with the pharmacokinetic parameters obtained. The bootstrap analysis provided parameter estimates within approximately 15% of the original estimates, indicating stability of the model. Conclusion: The pharmacokinetic behavior of KRN7000 in the clinical trial could be described by a three-compartment model. Hence, KRN7000 demonstrates linear pharmacokinetics over the investigated dose range. The pharmacokinetics of KRN7000 are not influenced by patient demographic or pathophysiological characteristics

Clinical pharmacology of the novel marine-derived anticancer agent Ecteinascidin 743 administered as a 1- and 3-h infusion in a phase I study

Ecteinascidin 743 (ET-743) is an anticancer agent derived from the Caribbean tunicate Ecteinascidia turbinata. In the present article, the pharmacokinetics and pharmacodynamics of ET-743 are described within a phase I study. Forty patients with solid tumors initially received ET-743 as a 1-h i.v. infusion every 21 days at nine dose levels (50-1100 microg/m(2)). The maximal tolerated dose (MTD) was 1100 microg/m(2), with thrombocytopenia and fatigue as dose-limiting toxicities (DLTs). As this MTD was substantially lower than in parallel phase I studies, dose escalation continued using a prolonged, 3-h infusion. Thirty-two patients were entered at five dose levels (1000-1800 microg/m(2)). The MTD was 1800 microg/m(2) with pancytopenia and fatigue as DLTs. The recommended phase II dose was 1650 microg/m(2) given over 3 h at which 12 patients were treated. Pharmacokinetic monitoring was performed for both treatment schedules. Non-compartmental pharmacokinetic parameters at the recommended dose with the 3-h infusion were (mean value+/-SD): clearance 87+/-30 l/h and mean elimination half-life 26+/-7 h. Pharmacokinetics were linear at the dose range tested with this schedule. The percentage decrease in platelets, white blood cells and neutrophils correlated with the area under the plasma concentration versus time curve (AUC), dose and maximal plasma concentration (C(max)). Hepatic toxicity increased with dose, AUC and C(max). Administration of 1650 microg/m(2) ET-743 over 3 h seemed clinically feasible; pharmacokinetics were linear with this schedule. Hepatic and hematological toxicities correlated with exposure to ET-74