Emneord:
Pharmacokinetics,
Pharmacodynamics,
Pharmacology,
Pharmacometrics,
Therapeutic drug monitoring,
Clinical Pharmacy
Publikasjoner
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Kamp, Jasper; Zwart, Tom C.; Meziyerh, Soufian; Boog, Paul J. M. van der; Nijgh, Esther E. & Duin, Koen van
[Vis alle 8 forfattere av denne artikkelen]
(2023).
Meltdose Tacrolimus Population Pharmacokinetics and Limited Sampling Strategy Evaluation in Elderly Kidney Transplant Recipients.
Pharmaceutics.
16(1),
s. 17–17.
doi:
10.3390/pharmaceutics16010017.
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Background: Meltdose tacrolimus (Envarsus®) has been marketed as a formulation achieving a more consistent tacrolimus exposure. Due to the narrow therapeutic window of tacrolimus, dose individualization is essential. Relaxation of the upper age limits for kidney transplantations has resulted in larger numbers of elderly patients receiving tacrolimus. However, due to the physiological changes caused by aging, the tacrolimus pharmacokinetics (PK) might be altered. The primary aim was to develop a population PK model in elderly kidney transplant recipients. Secondary aims were the development and evaluation of a limited sampling strategy (LSS) for AUC estimation. Methods: A total of 34 kidney transplant recipients aged ≥65 years, starting on meltdose tacrolimus directly after transplantation, were included. An eight-point whole blood AUC0–24h and an abbreviated dried blood spot (DBS) AUC0–24h were obtained. The PK data were analyzed using nonlinear mixed effect modeling methods. Results: The PK data were best described using a two-compartment model, including three transit compartments and a mixture model for oral absorption. The best three-sample LSS was T = 0, 2, 6 h. The best four-sample LSSs were T = 0, 2, 6, 8 h and T = 0, 1, 6, 8 h. Conclusions: The developed population PK model adequately described the tacrolimus PK data in a population of elderly kidney transplant recipients. In addition, the developed population PK model and LSS showed an adequate estimation of tacrolimus exposure, and may therefore be used to aid in tacrolimus dose individualization.
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Olofsen, Erik; Kamp, Jasper; Henthorn, Thomas K.; Velzen, Monique van; Niesters, Marieke & Sarton, Elise
[Vis alle 7 forfattere av denne artikkelen]
(2022).
Ketamine Psychedelic and Antinociceptive Effects Are Connected.
Anesthesiology.
ISSN 0003-3022.
136(5),
s. 801–801.
doi:
10.1097/aln.0000000000004176.
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Background Ketamine produces potent analgesia combined with psychedelic effects. It has been suggested that these two effects are associated and possibly that analgesia is generated by ketamine-induced dissociation. The authors performed a post hoc analysis of previously published data to quantify the pharmacodynamic properties of ketamine-induced antinociception and psychedelic symptoms. The hypothesis was that ketamine pharmacodynamics ( i.e. , concentration–effect relationship as well as effect onset and offset times) are not different for these two endpoints. Methods Seventeen healthy male volunteers received escalating doses of S - and racemic ketamine on separate occasions. Before, during, and after ketamine infusion, changes in external perception were measured together with pain pressure threshold. A population pharmacokinetic–pharmacodynamic analysis was performed that took S - and R -ketamine and S - and R -norketamine plasma concentrations into account. Results The pharmacodynamics of S -ketamine did not differ for antinociception and external perception with potency parameter (median [95% CI]) C 50 , 0.51 (0.38 to 0.66) nmol/ml; blood-effect site equilibration half-life, 8.3 [5.1 to 13.0] min), irrespective of administration form (racemic ketamine or S -ketamine). R -ketamine did not contribute to either endpoint. For both endpoints, S -norketamine had a small antagonistic effect. Conclusions The authors conclude that their data support an association or connectivity between ketamine analgesia and dissociation. Given the intricacies of the study related to the pain model, measurement of dissociation, and complex modeling of the combination of ketamine and norketamine, it is the opinion of the authors that further studies are needed to detect functional connectivity between brain areas that produce the different ketamine effects. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New
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Kamp, Jasper; Velzen, Monique van; Aarts, Leon; Niesters, Marieke; Dahan, Albert & Olofsen, Erik
(2021).
Stereoselective ketamine effect on cardiac output: a population pharmacokinetic/pharmacodynamic modelling study in healthy volunteers.
British Journal of Anaesthesia.
ISSN 0007-0912.
127(1),
s. 23–31.
doi:
10.1016/j.bja.2021.02.034.
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Kamp, Jasper; Olofsen, Erik; Henthorn, Thomas K.; Velzen, Monique van; Niesters, Marieke & Dahan, Albert
(2020).
Ketamine Pharmacokinetics.
Anesthesiology.
ISSN 0003-3022.
133(6),
s. 1192–1213.
doi:
10.1097/aln.0000000000003577.
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Background Several models describing the pharmacokinetics of ketamine are published with differences in model structure and complexity. A systematic review of the literature was performed, as well as a meta-analysis of pharmacokinetic data and construction of a pharmacokinetic model from raw data sets to qualitatively and quantitatively evaluate existing ketamine pharmacokinetic models and construct a general ketamine pharmacokinetic model. Methods Extracted pharmacokinetic parameters from the literature (volume of distribution and clearance) were standardized to allow comparison among studies. A meta-analysis was performed on studies that performed a mixed-effect analysis to calculate weighted mean parameter values and a meta-regression analysis to determine the influence of covariates on parameter values. A pharmacokinetic population model derived from a subset of raw data sets was constructed and compared with the meta-analytical analysis. Results The meta-analysis was performed on 18 studies (11 conducted in healthy adults, 3 in adult patients, and 5 in pediatric patients). Weighted mean volume of distribution was 252 l/70 kg (95% CI, 200 to 304 l/70 kg). Weighted mean clearance was 79 l/h (at 70 kg; 95% CI, 69 to 90 l/h at 70 kg). No effect of covariates was observed; simulations showed that models based on venous sampling showed substantially higher context-sensitive half-times than those based on arterial sampling. The pharmacokinetic model created from 14 raw data sets consisted of one central arterial compartment with two peripheral compartments linked to two venous delay compartments. Simulations showed that the output of the raw data pharmacokinetic analysis and the meta-analysis were comparable. Conclusions A meta-analytical analysis of ketamine pharmacokinetics was successfully completed despite large heterogeneity in study characteristics. Differences in output of the meta-analytical approach and a combined analysis of 14 raw data sets were small, indicative that the meta-analytical approach gives a clinically applicable approximation of ketamine population parameter estimates and may be used when no raw data sets are available. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New
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Kamp, Jasper; Velzen, Monique Van; Olofsen, Erik; Boon, Martijn; Dahan, Albert & Niesters, Marieke
(2019).
Pharmacokinetic and pharmacodynamic considerations for NMDA-receptor antagonist ketamine in the treatment of chronic neuropathic pain: an update of the most recent literature.
Expert Opinion on Drug Metabolism & Toxicology.
ISSN 1742-5255.
15(12),
s. 1033–1041.
doi:
10.1080/17425255.2019.1689958.
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Bahar, Muh. Akbar; Kamp, Jasper; Borgsteede, Sander D.; Hak, Eelko & Wilffert, Bob
(2018).
The impact of CYP2D6 mediated drug–drug interaction: a systematic review on a combination of metoprolol and paroxetine/fluoxetine.
British Journal of Clinical Pharmacology.
ISSN 0306-5251.
84(12),
s. 2704–2715.
doi:
10.1111/bcp.13741.
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Aim Metoprolol (a CYP2D6 substrate) is often co‐prescribed with paroxetine/fluoxetine (a CYP2D6 inhibitor) because the clinical relevance of this drug–drug interaction (DDI) is still unclear. This review aimed to systematically evaluate the available evidence and quantify the clinical impact of the DDI. Method Pubmed, Web of Science, Cochrane Library and Embase were searched for studies reporting on the effect of the DDI among adults published until April 2018. Data on pharmacokinetics, pharmacodynamics and clinical outcomes from experimental, observational and case report studies were retrieved. The protocol of this study was registered in PROSPERO (CRD42018093087). Results We found nine eligible articles that consisted of four experimental and two observational studies as well as three case reports. Experimental studies reported that paroxetine increased the AUC of metoprolol three to five times, and significantly decreased systolic blood pressure and heart rate of patients. Case reports concerned bradycardia and atrioventricular block due to the DDI. Results from observational studies were conflicting. A cohort study indicated that the DDI was significantly associated with the incidence of early discontinuation of metoprolol as an indicator of the emergence of metoprolol‐related side effects. In a case–control study, the DDI was not significantly associated with bradycardia. Conclusion Despite the contradictory conclusions from the current literature, the majority of studies suggest that the DDI can lead to adverse clinical consequences. Since alternative antidepressants and beta‐blockers with comparable efficacy are available, such DDIs can be avoided. Nonetheless, if prescribing the combination is unavoidable, a dose adjustment or close monitoring of the metoprolol‐related side effects is necessary.
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Publisert
17. okt. 2025 06:54
- Sist endret
1. des. 2025 13:41
