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  • 1
    Electronic Resource
    Electronic Resource
    Amount of self-reported illicit drug use compared to quantitative hair test results in community-recruited young drug users in Amsterdam (2003)
    Oxford, UK : Blackwell Science Ltd
    Addiction 98 (2003), S. 0 
    Details
    ISSN: 1360-0443
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine , Psychology
    Notes: Aims  To assess the dose–effect relationship between self-reported drug intake and the concentration of drugs and/or their metabolites in hair and to examine factors that may mediate this relationship.Design and setting  A cohort study among young drug users (YDU) in Amsterdam, the Netherlands, which began in July 2000. At intake, YDU were asked to report their average drug intake over a 2-month period. A hair sample was taken and then analysed for cocaine, benzoylecgonine (BE), morphine, 6-monoacetylmorphine and methadone. Weighted least-squares regression analysis was used to model hair-test results as a function of reported drug use.Participants  Subjects were 95 YDU (using cocaine, heroin, methadone and/or amphetamines at least 3 days/week) aged 18–30 residing in Amsterdam in 2000–2001.Findings  Of the 95 YDU, one-third were women; mean age was almost 26; 30% had black hair, 33% blond hair and 37% brown hair. Cocaine use was reported by 92%, heroin by 75% and methadone by 64% of participants. All hair samples contained one or more drugs. Crude correlation coefficients between reported drug doses and drug concentrations in hair ranged between 0.45 and 0.59. The multivariate regression analysis showed that, for one or more types of drug, black-haired people, women and non-western European people had relatively high drug concentrations in hair (significant slope effects). The corresponding multivariate correlation coefficients ranged between 0.63 and 0.87.Conclusions  Hair testing can be used to quantify drug use in epidemiological studies, given that factors such as hair colour and sex are taken into account.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1360-0443.2003.00421.x
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  • 2
    Electronic Resource
    Electronic Resource
    Validation of a limited sampling model for carboplatin in a high-dose chemotherapy combination (1994)
    Springer
    Cancer chemotherapy and pharmacology 35 (1994), S. 179-181 
    Details
    ISSN: 1432-0843
    Keywords: Key words Carboplatin ; Limited sampling ; Validation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A limited sampling model for the estimation of the carboplatin area under the concentration versus time curve (AUC), as developed by Sørensen et al., was validated prospectively for the use in a high-dose combination chemotherapy schedule. The model allows an estimation of the AUC on the basis of only one timed plasma drug concentration, sampled at exactly 2.75 h after a 1-h carboplatin infusion. Pharmacokinetic curves were obtained from nine patients receiving carboplatin (400 mg/m2 per day) combined with cyclophosphamide (1500 mg/m2 per day), thiotepa (120 mg/m2 per day), and mesna (3 g/day) for 4 consecutive days. Peripheral blood stem-cell transplantation (PBSCT) was performed 3 days later to restore hematopoiesis. Using this combination of high doses, the model proved to be unbiased (MPE –3.40%; SE, 1.22%) and highly precise [root mean squared prediction error (RMSE), 5.15%; SE, 0.17%] for estimation of the AUC during 4 consecutive days. The validated limited sampling model provides a starting point for future pharmacokinetic studies in a larger population of patients, which might lead to more insight into the relationships with the pharmacodynamic outcome of carboplatin and may help in achieving more rational dosing of patients on the basis of an AUC determination.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00686644
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  • 3
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and pharmacodynamics of topotecan administered daily for 5 days every 3 weeks (1995)
    Springer
    Cancer chemotherapy and pharmacology 35 (1995), S. 237-245 
    Details
    ISSN: 1432-0843
    Keywords: Pharmacodynamics ; Pharmacokinetics ; Topotecan ; Topoisomerase I inhibitor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Topotecan is a novel semisynthetic derivative of the anticancer agent camptothecin and inhibits the intranuclear enzyme topoisomerase I. The lactone structure of topotecan, which is in equilibrium with the inactive ringopened hydroxy acid, is essential for this activity. The open form predominates at physiological pH. We performed a pharmacokinetic, study as part of a phase I study in patients with various types of solid tumors, where topotecan was administered in a 30-min infusion daily on 5 consecutive days every 3 weeks. The plasma kinetics of topotecan could be described best using an open two-compartment model with t1/2(α) and t1/2(β) of 8.1 (range 0.3 to 40.7) min and 132 (range 49 to 286) min, respectively. The plasma concentration-time profiles of the metabolite, however, could be described using a one-compartment model with t1/2(formation) of 29.0 (range 5.6–99.5) min and t1/2 (elimination of 123.2 (range 32–265) min, respectively. The lactone was the predominate form during the first hour from the start of infusion, but was rapidly converted into its ring-opened structure. The elimination rate of topotecan was independent of the dose. There were linear relationships between the dose (mg m−2 day−1), the area under the plasma concentration versus time curve (AUC) of topotecan and its metabolite, the total AUC, peak plasma lactone concentrations, and the time period that the topotecan concentrations remained above 10 nM. Different models were used to correlate pharmacokinetic and pharmacodynamic parameters. The percentage decrease in absolute neutrophil count (ANC) was related to these parameters and plots were well fitted by linear and sigmoidal Emax models.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00686554
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  • 4
    Electronic Resource
    Electronic Resource
    Validation of a limited sampling model for carboplatin in a high-dose chemotherapy combination (1994)
    Springer
    Cancer chemotherapy and pharmacology 35 (1994), S. 179-181 
    Details
    ISSN: 1432-0843
    Keywords: Carboplatin ; Limited sampling ; Validation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A limited sampling model for the estimation of the carboplatin area under the concentration versus time curve (AUC), as developed by Sørensen et al., was validated prospectively for the use in a high-dose combination chemotherapy schedule. The model allows an estimation of the AUC on the basis of only one timed plasma drug concentration, sampled at exactly 2.75 h after a 1-h carboplatin infusion. Pharmacokinetic curves were obtained from nine patients receiving carboplatin (400 mg/m2 per day) combined with cyclophosphamide (1500 mg/m2 per day), thiotepa (120 mg/m2 per day), and mesna (3 g/day) for 4 consecutive days. Peripheral blood stem-cell transplantation (PBSCT) was performed 3 days later to restore hematopoiesis. Using this combination of high doses, the model proved to be unbiased (MPE −3.40%; SE, 1.22%) and highly precise [root mean squared prediction error (RMSE), 5.15%; SE, 0.17%] for estimation of the AUC during 4 consecutive days. The validated limited sampling model provides a starting point for future pharmacokinetic studies in a larger population of patients, which might lead to more insight into the relationships with the pharmacodynamic outcome of carboplatin and may help in achieving more rational dosing of patients on the basis of an AUC determination.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00686644
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  • 5
    Electronic Resource
    Electronic Resource
    Evaluation of formulas using the serum creatinine level to calculate the optimal dosage of carboplatin (1995)
    Springer
    Cancer chemotherapy and pharmacology 37 (1995), S. 266-270 
    Details
    ISSN: 1432-0843
    Keywords: AUC ; Carboplatin ; Pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Carboplatin is a chemotherapeutic agent frequently used in the treatment of various malignancies. An individual dosing strategy has been recommended to yield the most optimal exposure, expressed as the area under the concentration-time curve (AUC). The formula developed by Calvert et al. (dose = target-AUC × [GFR+25]) can be used to achieve this. However, due to the inconvenient [51Cr]-ethylenediaminetetraacetic acid ([51Cr]-EDTA)-based measurement of the glomerular filtration rate (GFR), its application in the clinic has thus far been limited. Chatelut and coworkers have recently proposed a formula to estimate carboplatin clearance using the serum creatinine concentration. We retrospectively tested the Chatelut equation and the Calvert formula using either the creatinine clearance based on 24-h urine collection or the creatinine clearance based on the formula of Cockcroft and Gault. The latter equations were shown to predict the carboplatin clearance reasonably well, although systematic overprediction and underprediction occurred. However, the formula proposed by Chatelut and co-workers had no significant bias and was precise. It is proposed that this formula be used to calculate the optimal carboplatin dosage after prospective validation has been performed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00688327
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  • 6
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and pharmacodynamics of topotecan given on a daily-times-five schedule in phase II clinical trials using a limited-sampling procedure (1996)
    Springer
    Cancer chemotherapy and pharmacology 38 (1996), S. 254-260 
    Details
    ISSN: 1432-0843
    Keywords: Key words Limited-sampling model ; Pharmacodynamics ; Pharmacokinetics ; Phase II ; Topotecan
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Topotecan is a novel semisynthetic derivative of the anticancer agent camptothecin and inhibits the intranuclear enzyme topoisomerase I. The lactone structure of topotecan, which is in equilibrium with the inactive ring-opened hydroxy acid, is essential for this activity. We performed a pharmacokinetics study as part of phase II clinical trials in patients with various types of solid tumors, giving topotecan at 1.5 mg/m2 per day by 30-min infusion for 5 consecutive days, with courses being repeated every 3 weeks. Previously validated limited-sampling models, using concentration measurements in samples obtained 2 h after infusion, were used to calculate the area under the plasma concentration-time curves (AUCs) for both chemical forms. Samples were obtained from a total of 36 patients over 136 treatment days. The mean AUC of the closed-ring form (AUCclosed) was 8.74 (range 2.3–16.3)  μM min per day, and the mean AUC of the ring-opened form (AUCopen) was 11.5 (range 3.2–46.0)  μM min per day (interpatient variability 34–61%). In each patient the AUC values achieved on the 1st day of administration were similar to and, thus, predictive for those achieved during the following days, with a day-to-day variation of 7.39% being recorded for the AUCclosed and that of 12.6%, for the AUCopen. There was no drug accumulation during the 5 consecutive treatment days of each cycle. However, despite the large interpatient pharmacokinetic variability, the importance of regular drug monitoring on this schedule can be questioned, as the pharmacodynamic variability was relatively small.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002800050479
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  • 7
    Electronic Resource
    Electronic Resource
    Radioiodinated metaiodobenzylguanidine: a review of its biodistribution and pharmacokinetics, drug interactions, cytotoxicity and dosimetry (1994)
    Springer
    European journal of nuclear medicine 21 (1994), S. 545-559 
    Details
    ISSN: 1619-7089
    Keywords: Biodistribution ; Cytotoxicity ; Dosimetry ; Pharmacokinetics ; Radioiodinated metaiodobenzylguanidine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Since the introduction of radioiodinated metaiodobenzylguanidine in 1980, considerable research has been performed, both in the chemical field and in medical sciences. However, despite the wide use of radioiodinated metaiodobenzylguanidine, knowledge about its pharmacology is still limited. This paper reviews the biodistribution and pharmacokinetics, drug interactions, cytotoxicity and dosimetry of radioiodinated metaiodobenzylguanidine. Iodine-131 metaiodobenzylguanidine therapy is in general well tolerated, but its effectiveness needs improvement. Also whole-body dosimetry as part of treatment planning needs to be improved. Future prospects on these items are included in this review.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00173043
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  • 8
    Electronic Resource
    Electronic Resource
    Discriminative stimulus properties of mCPP: evidence for a 5-HT2C receptor mode of action (1998)
    Springer
    Psychopharmacology 137 (1998), S. 292-302 
    Details
    ISSN: 1432-2072
    Keywords: Key words mCPP (m-chlorophenylpiperazine) ; Drug discrimination ; 5-HT2C ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous drug discrimination studies with the serotonergic drug m-chlorophenylpiperazine (mCPP) showed conflicting results, with some authors concluding that the cue was mediated by 5-HT2C receptors, but others that it was definitively not. We further examined the discriminative stimulus properties of mCPP in rats and reviewed previously published data. We trained rats to discriminate mCPP (2.0 mg/kg, PO) from water. We found that the mCPP cue generalized to m-trifluoromethyl-phenylpiperazine (TFMPP) and 6-chloro-2-(1-piperazinyl)-pyrazine (MK-212), and partially to eltoprazine, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), fenfluramine and trazodone. A moderate level of generalization was obtained with quipazine, 1-(m-chlorophenyl)biguanide and clonidine. No generalization was found with flesinoxan, methiothepin, idazoxan and haloperidol. Mianserin and methysergide antagonized the mCPP stimulus, whereas ketanserin antagonized it partially. Metergoline, methiothepin and clozapine only marginally antagonized the mCPP stimulus. These results show that the discriminative stimulus effects of mCPP are predominantly mediated by 5-HT2C receptors, and to some extent by 5-HT1B receptors. When considering our results and other research together, the substitution tests clearly point to a 5-HT2C receptor mediated stimulus, with an additional role for 5-HT1B receptors. Antagonism studies are less clearcut, but are also suggestive of a 5-HT2C receptor mediated effect. A definitive answer as to whether other receptors, e.g. 5-HT2B and 5-HT7, are of any importance in mCPP’s discriminative stimulus properties has to wait for more selective ligands.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050622
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  • 9
    Electronic Resource
    Electronic Resource
    Discriminative stimulus properties of alprazolam (2000)
    Springer
    Psychopharmacology 148 (2000), S. 146-152 
    Details
    ISSN: 1432-2072
    Keywords: Key words Alprazolam ; Drug discrimination ; Benzodiazepines ; Antidepressant ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: The triazolobenzodiazepine alprazolam has a unique clinical profile compared to most other benzodiazepines (e.g. diazepam, chlordiazepoxide), in that it is used to treat panic disorder and is effective in depression, two disorders that are usually treated with anti-depressants. Previous drug discrimination studies suggested that alprazolam has stimulus properties in common with antidepressants. Objective: In the present study, the discriminative stimulus properties of alprazolam were investigated to test more conclusively the role of benzodiazepine receptors and whether alprazolam has stimulus properties in common with antidepressants. Methods: Male Wistar rats (n=12) were trained to discriminate between alprazolam (2.0 mg/kg, PO) and vehicle in an operant two-lever drug discrimination procedure under a tandem VI40”-FR10 schedule of reinforcement. Generalization and antagonism tests were carried out under 2 min extinction. Results: In generalization tests, a number of benzodiazepines (alprazolam, chlordiazepoxide, midazolam, lorazepam) and the barbiturate pentobarbital substituted completely, while zolpidem and abecarnil substituted partially for alprazolam. In contrast, no significant degree of generalization to the antidepressants imipramine and fluvoxamine and the putative antidepressants buspirone and flesinoxan was found. In antagonism studies alprazolam could be antagonized (almost) completely by flumazenil, partially by pentylenetetrazole, but not by methyl 6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate (DMCM), N-methyl-β-carboline-3-carboxamide (FG-7142) and picrotoxin. Conclusions: These results show that the discriminative stimulus properties of alprazolam are mediated by benzodiazepine receptors and that the finding that antidepressants share discriminative stimulus effects with alprazolam may have limited generality.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050036
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  • 10
    Electronic Resource
    Electronic Resource
    Flesinoxan pretreatment differentially affects corticosterone, prolactin and behavioural responses to a flesinoxan challenge (1997)
    Springer
    Psychopharmacology 131 (1997), S. 93-100 
    Details
    ISSN: 1432-2072
    Keywords: Key words 5-HT1A ; Anxiety ; Corticosterone ; Prolactin ; Defensive burying ; Flesinoxan ; Repeated drug administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To determine whether alterations in 5-HT1A receptor mediated responses induced by a single injection with a selective 5-HT1A receptor agonist is a transient effect, or whether the (de)sensitisation is more persistent, rats were pretreated with the selective and full 5-HT1A receptor agonist, flesinoxan (3 mg/kg SC once daily) for either 1 day or 1 week. Twenty-four hour after the last pretreatment injection, rats were challenged with flesinoxan (3 mg/kg SC), and the effects on plasma corticosterone and prolactin levels, lower lip retraction and behaviour in the shock-probe burying test were determined. Several 5-HT1A receptor mediated responses were modified differentially following the flesinoxan pretreatment. However, all changes induced by a single flesinoxan injection remained present upon repeated flesinoxan administration. The differential changes in the responses to flesinoxan cannot easily be explained by differences in pre-or postsynaptically 5-HT1A mediated responses. The prolactin response to flesinoxan, which is thought to be mediated postsynaptically, was enhanced, whereas the corticosterone response to flesinoxan, which is also mediated postsynaptically, was attenuated. The presynaptically mediated lower lip retraction response was attenuated as well, whereas the behavioural effects of flesinoxan remained relatively unaffected following repeated flesinoxan administration. Upon prolonged flesinoxan pretreatment, the changes induced by a single flesinoxan injection remained present or increased further. Although repeated flesinoxan administration (1 day and 1 week) resulted in 20% lower plasma flesinoxan concentrations, this effect could not explain the neuroendocrine and behavioural findings.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050270
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