32 research outputs found
ICT: New Opportunities for Higher Education Institutions to Train Employees?
Higher education institutions are confronted with a declining growth in the number of students in initial education. At the same time, the market for training of employees has increased significantly. Between 1993 and 1999, the total training volume on this market has doubled. However, at least in the Netherlands, higher education institutes altogether have only a small and stable share in the training of employees of about 2%.
The central question of this paper is to what extent the growing possibilities of using ICT as a training tool can help higher education institutes to enhance their position in the market of training of employees. The empirical evidence presented does not support the expectation that ICTis already the vehicle leading to drastic changes. A large scale survey among companies at the end of the nineties in the Netherlands showed that the use of ICT as a training tool was at that time limited to only 12% of all training incidences. Moreover, the companies did not expect a strong growth. This has to do with a large variety of bottlenecks companies perceive. Succesful implementation means dealing with considerations from many angles: pedagogical, technical, organisational and last but least cost-efficiency.
Even if the use of ICT as a training tool would rise considerable, this would not automatically mean an improvement of the position of higher education institutes. The survey results do not give indications that higher education institutions have a relative large share in ICT-based training.In: A.J. Kallenberg and M.J.J.M. van de Ven (Eds), 2002, The New Educational Benefits of ICT in Higher Education: Proceedings. Rotterdam: Erasmus Plus BV, OECR
ISBN 90-9016127-
Topotecan lacks third space sequestration
The objective of this study was to determine the influence of pleural and
ascitic fluid on the pharmacokinetics of the antitumor camptothecin
derivative topotecan. Four patients with histological proof of malignant
solid tumor received topotecan (0.45 or 1.5 mg/m2) p.o. on several
occasions in both the presence and absence of third space volumes. Serial
plasma and pleural or ascitic fluid samples were collected during each
dosing and analyzed by high-performance liquid chromatography for both the
intact lactone form of topotecan and its ring-opened carboxylate form. The
apparent topotecan clearance demonstrated substantial interpatient
variability but remained unchanged within the same patient in the presence
[110 +/- 55.6 liters/ h/m2 (mean +/- SD of eight courses)] or absence of
pleural and ascitic fluid [118 +/- 31.1 liters/h/m2 (mean +/- SD of seven
courses)]. Similarly, terminal half-lives and area under the
concentration-time curve ratios of lactone:total drug in plasma were
similar between courses within each patient. Topotecan penetration into
pleural and ascitic fluid demonstrated a mean lag time of 1.61 h (range,
1.37-1.86 h), and ratios with plasma concentration increased with time
after dosing in all patients. The mean ratio of third space topotecan
total drug area under the concentration-time curve to that in plasma was
0.55 (range, 0.26-0.87). These data indicate that topotecan can be safely
administered to patients with pleural effusions or ascites and that there
is substantial penetration of topotecan into these third spaces, which may
prove beneficial for local antitumor effects
Inter- and intrapatient variability in oral topotecan pharmacokinetics: implications for body-surface area dosage regimens
Anticancer drugs still are dosed based on the body-surface area (BSA) of
the individual patient, although the BSA is not the main predictor of the
clearance for the majority of drugs. The relevance of BSA-based dosing has
not been evaluated for topotecan yet. A retrospective pharmacological
analysis was performed of kinetic data from four clinical Phase I studies
in which topotecan was administered p.o. as a single agent combined with
data from a combination study of topotecan and cisplatin. A strong
correlation (r = 0.91) was found between the area under the plasma
concentration time curve of the lactone and carboxylate forms of topotecan
by plotting 326 data sets obtained from 112 patients receiving oral
topotecan at dose levels ranging from 0.15-2.70 mg/m2. The intrapatient
variability, studied in 47 patients sampled for 3 or more days, for the
apparent lactone clearance, ranged from 7.4-69% (mean, 24 +/- 13%; median,
20%). The interpatient variabilities in the lactone clearance, calculated
with the data of all studied patients, expressed in liter/h/m2 and in
liter/h were 38% and 42%, respectively. In view of the relatively high
inter- and intrapatient variabilities in topotecan clearance, in contrast
to a variability of only 12% in the BSA of the studied patients, no
advantage of BSA-based dosing was found over fixed dose regimens
Influence of Cremophor El on the bioavailability of intraperitoneal paclitaxel
It has been hypothesized that the paclitaxel vehicle Cremophor EL (CrEL)
is responsible for nonlinear drug disposition by micellar entrapment. To
gain further insight into the role of CrEL in taxane pharmacology, we
studied the pharmacokinetics of paclitaxel in the presence and absence of
CrEL after i.p. and i.v. dosing. Patients received an i.p. tracer dose of
[G-(3)H]paclitaxel in ethanol without CrEL (100 microCi diluted further in
isotonic saline) on day 1, i.p. paclitaxel formulated in CrEL (Taxol; 125
mg/m(2)) on day 4, an i.v. tracer of [G-(3)H]paclitaxel on day 22, and
i.v. Taxol (175 mg/m(2)) on day 24. Four patients (age range, 54-74 years)
were studied, and serial plasma samples up to 72 h were obtained and
analyzed for total radioactivity, paclitaxel, and CrEL. In the presence of
CrEL, i.v. paclitaxel clearance was 10.2 +/- 3.76 liters/h/m(2) (mean +/-
SD), consistent with previous findings. The terminal disposition half-life
was substantially prolonged after i.p. dosing (17.0 +/- 11.3 versus 28.7
+/- 8.72 h), as was the mean residence time (7.28 +/- 2.76 versus 40.7 +/-
13.8 h). The bioavailability of paclitaxel was 31.4 +/- 5.18%, indicating
insignificant systemic concentrations after i.p. treatment. CrEL levels
were undetectable after i.p. dosing (<0.05 microl/ml), whereas after i.v.
dosing, the mean clearance was 159 +/- 58.4 ml/h/m(2), in line with
earlier observations. In the absence of CrEL, the bioavailability and
systemic concentrations of i.p. paclitaxel were significantly increased.
This finding is consistent with the postulated concept that CrEL is
largely responsible for the pharmacokinetic advantage for peritoneal
cavity exposure to total paclitaxel compared with systemic delivery
Disposition of [G-(3)H]paclitaxel and cremophor EL in a patient with severely impaired renal function
In the present work, we studied the pharmacokinetics and metabolic
disposition of [G-(3)H]paclitaxel in a female patient with recurrent
ovarian cancer and severe renal impairment (creatinine clearance:
approximately 20 ml/min) due to chronic hypertension and prior cisplatin
treatment. During six 3-weekly courses of paclitaxel at a dose level of
157.5 mg/m(2) (viz. a 10% dose reduction), the renal function remained
stable. Pharmacokinetic evaluation revealed a reproducible and
surprisingly high paclitaxel area under the plasma concentration-time
curve of 26.0 +/- 1.11 microM.h (mean +/- S.D.; n = 6; c.v. = 4.29%), and
a terminal disposition half-life of approximately 29 h. Both parameters
are substantially increased ( approximately 1.5-fold) when compared with
kinetic data obtained from patients with normal renal function. The
cumulative urinary excretion of the parent drug was consistently low and
averaged 1.58 +/- 0.417% (+/- S.D.) of the dose. Total fecal excretion
(measured in one course) was 52.9% of the delivered radioactivity, and
mainly comprised known mono- and dihydroxylated metabolites, with
unchanged paclitaxel accounting for only 6.18%. The plasma area under the
plasma concentration-time curve of the paclitaxel vehicle Cremophor EL,
which can profoundly alter the kinetics of paclitaxel, was 114.9 +/- 5.39
microl.h/ml, and not different from historic data in patients with normal
or mild renal dysfunction. Urinary excretion of Cremophor EL was less than
0.1% of the total amount administered. These data indicate that the
substantial increase in systemic exposure of the patient to paclitaxel
relates to decreased renal metabolism and/or urinary elimination of polar
radioactive species, most likely lacking an intact taxane ring fragment