Four open mammillary and catenary compartment models for pharmacokinetics studies

Biasi, J. De

doi:10.1016/0141-5425(89)90041-1

Cited by 10 publications

(3 citation statements)

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“… 36 , 37 A total of 5414 midazolam concentrations corresponding to 306 unique 24‐h pharmacokinetic profiles were available from a total of 98 patients. A catenary three‐compartment model 38 , 39 with absorption lag‐time and first‐order elimination from the central compartment (Figure S1 ) was developed and validated. Due to the sole interest in individual predictions of pharmacokinetic parameters and to avoid including the same potential covariate both in the pharmacokinetic population model and the statistical analysis (linear mixed effects model), no covariates were implemented in the population model.…”

Section: Methodsmentioning

confidence: 99%

Short‐ and long‐term effects of body weight loss following calorie restriction and gastric bypass on CYP3A‐activity – a non‐randomized three‐armed controlled trial

Kvitne

Robertsen

Skovlund

et al. 2021

Clinical Translational Sci

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It remains uncertain whether pharmacokinetic changes following Roux‐en‐Y gastric bypass (RYGB) can be attributed to surgery‐induced gastrointestinal alterations per se and/or the subsequent weight loss. The aim was to compare short‐ and long‐term effects of RYGB and calorie restriction on CYP3A‐activity, and cross‐sectionally compare CYP3A‐activity with normal weight to overweight controls using midazolam as probe drug. This three‐armed controlled trial included patients with severe obesity preparing for RYGB ( n = 41) or diet‐induced ( n = 41) weight‐loss, and controls ( n = 18). Both weight‐loss groups underwent a 3‐week low‐energy‐diet (<1200 kcal/day) followed by a 6‐week very‐low‐energy‐diet or RYGB (both <800 kcal/day). Patients were followed for 2 years, with four pharmacokinetic investigations using semisimultaneous oral and intravenous dosing to determine changes in midazolam absolute bioavailability and clearance, within and between groups. The RYGB and diet groups showed similar weight‐loss at week 9 (13 ± 2.4% vs. 11 ± 3.6%), but differed substantially after 2 years (−30 ± 7.0% vs. −3.1 ± 6.3%). At baseline, mean absolute bioavailability and clearance of midazolam were similar in the RYGB and diet groups, but higher compared with controls. On average, absolute bioavailability was unaltered at week 9, but decreased by 40 ± 7.5% in the RYGB group and 32 ± 6.1% in the diet group at year 2 compared with baseline, with no between‐group difference. No difference in clearance was observed over time, nor between groups. In conclusion, neither RYGB per se nor weight loss impacted absolute bioavailability or clearance of midazolam short term. Long term, absolute bioavailability was similarly decreased in both groups despite different weight loss, suggesting that the recovered CYP3A‐activity is not only dependent on weight‐loss through RYGB.

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Section: Methodsmentioning

confidence: 99%

Short‐ and long‐term effects of body weight loss following calorie restriction and gastric bypass on CYP3A‐activity – a non‐randomized three‐armed controlled trial

Kvitne

Robertsen

Skovlund

et al. 2021

Clinical Translational Sci

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“…For brain PET receptor studies the established catenary tracer kinetic model consists of one extracerebral compartment represented by blood and two intracerebral compartments represented by nonspecific (nonreceptor) binding and specific (receptor) binding. In early brain receptor studies a mammillary model [15] was proposed which included four compartments: (1) an extracellular free radioligand compartment which was connected via bidirectional tracer transfer with three additional compartments, (2) plasma, (3) nonspecific binding sites, and (4) specific binding sites [4]. The four-compartmental model was not applicable for most radioligands due to an insignificant difference between the turnover rates of the free ligand and the nonspecific binding compartments.…”

Section: Discussionmentioning

confidence: 99%

Modeling of the Renal Kinetics of the AT1 Receptor Specific PET Radioligand [¹¹C]KR31173

Gülaldı

Xia

Feng

et al. 2013

BioMed Research International

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Purpose. The radioligand [11C]KR31173 has been introduced for PET imaging of the angiotensin II subtype 1 receptor (AT1R). The purpose of the present project was to employ and validate a compartmental model for quantification of the kinetics of this radioligand in a porcine model of renal ischemia followed by reperfusion (IR). Procedures. Ten domestic pigs were included in the study: five controls and five experimental animals with IR of the left kidney. To achieve IR, acute ischemia was created with a balloon inserted into the left renal artery and inflated for 60 minutes. Reperfusion was achieved by deflation and removal of the balloon. Blood chemistries, urine specific gravity and PH values, and circulating hormones of the renin angiotensin system were measured and PET imaging was performed one week after IR. Cortical time-activity curves obtained from a 90 min [11C]KR31173 dynamic PET study were processed with a compartmental model that included two tissue compartments connected in parallel. Radioligand binding quantified by radioligand retention (80 min value to maximum value ratio) was compared to the binding parameters derived from the compartmental model. A binding ratio was calculated as DVR = DVS/DVNS, where DVS and DVNS represented the distribution volumes of specific binding and nonspecific binding. Receptor binding was also determined by autoradiography in vitro. Results. Correlations between rate constants and binding parameters derived by the convolution and deconvolution curve fittings were significant (r > 0.9). Also significant was the correlation between the retention parameter derived from the tissue activity curve (Y ret) and the retention parameter derived from the impulse response function (f ret). Furthermore, significant correlations were found between these two retention parameters and DVR. Measurements with PET showed no significant changes in the radioligand binding parameters caused by IR, and these in vivo findings were confirmed by autoradiography performed in vitro. Conclusions. Correlations between various binding parameters support the concept of the parallel connectivity compartmental model. If an arterial input function cannot be obtained, simple radioligand retention may be adequate for estimation of in vivo radioligand binding.

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“…The pharmacokinetic models [1][2][3] are used in drug concentration analysis in various biological compartments (plasma compartment, tissue compartment, deep-tissue compartment, and mammillary compartment). Among them, the mammillary compartment model is usually used for the drug distribution analysis in the biological body.…”

Section: Introductionmentioning

confidence: 99%

Untitled

2022

AJMS

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This paper deals with the application of Laplace Transform to estimate the fate of a drug in the mammillary body with the prediction of various biological parameters (k, k 12 , and k 21 ) through the method of residuals. The essential numerical values of k, k 12 , and k 21 are estimated through the determination of the mathematical hybrid constants (A, B, a, b, and T). Besides, these values can predict the tissue concentration (c t ) of the drug, and biological half-life (t 1/2 ) as well. Thus, this study provides intuitive information on the fate of the administered drug in a mammillary body, successfully.

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Four open mammillary and catenary compartment models for pharmacokinetics studies

Cited by 10 publications

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Short‐ and long‐term effects of body weight loss following calorie restriction and gastric bypass on CYP3A‐activity – a non‐randomized three‐armed controlled trial

Short‐ and long‐term effects of body weight loss following calorie restriction and gastric bypass on CYP3A‐activity – a non‐randomized three‐armed controlled trial

Modeling of the Renal Kinetics of the AT1 Receptor Specific PET Radioligand [¹¹C]KR31173

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Four open mammillary and catenary compartment models for pharmacokinetics studies

Cited by 10 publications

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Short‐ and long‐term effects of body weight loss following calorie restriction and gastric bypass on CYP3A‐activity – a non‐randomized three‐armed controlled trial

Short‐ and long‐term effects of body weight loss following calorie restriction and gastric bypass on CYP3A‐activity – a non‐randomized three‐armed controlled trial

Modeling of the Renal Kinetics of the AT1 Receptor Specific PET Radioligand [11C]KR31173

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Modeling of the Renal Kinetics of the AT1 Receptor Specific PET Radioligand [¹¹C]KR31173