Prediction of Drug Terminal Half-Life and Terminal Volume of Distribution After Intravenous Dosing Based on Drug Clearance, Steady-State Volume of Distribution, and Physiological Parameters of the Body

Berezhkovskiy, Leonid M.

doi:10.1002/jps.23396

Cited by 13 publications

(10 citation statements)

References 53 publications

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“…4 with that obtained from the terminal slope of C p ( t ) for rat, dog, monkey and human studies is shown in Figure 1. The references for pharmacokinetic data are provided in the original article 8. The calculated values of t 1/2 appear to be in a reasonably good agreement with the experimentally observed ones.…”

Section: Resultssupporting

confidence: 72%

“…The comparison of V β calculated by Eq. 8 with experimental values [obtained from C p ( t ) for rat, dog, monkey, and human studies8] is shown in Figure 2. The agreement between calculated and observed V β is quite well.…”

Section: Resultsmentioning

confidence: 98%

“…The terminal phase of drug elimination after i.v. dose was studied in a recent article considering two‐compartment physiological model 8. The following equation for the terminal log‐linear slope β = ln2/ t 1/2 of C p ( t ) was obtained where r is the equilibrium blood–plasma concentration ratio, Q is the cardiac output,1,9 V b is the blood volume of the body, k = rQ /( V ss − rV b ).…”

Section: Resultsmentioning

confidence: 99%

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On the Accuracy of a One-Compartment Approach for Determination of Drug Terminal Half-Life

Berezhkovskiy¹

2013

Journal of Pharmaceutical Sciences

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Section: Resultssupporting

confidence: 72%

Section: Resultsmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%

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On the Accuracy of a One-Compartment Approach for Determination of Drug Terminal Half-Life

Berezhkovskiy¹

2013

Journal of Pharmaceutical Sciences

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“…Nevertheless, the concentrations are great enough to carry out their expected pharmacological activity. If we consider that oral dexamethasone as an antiinflammatory agent in ocular conditions is approved for a 2mg daily dose [14], and that the volume of distribution at the steady state V ss is about 1 l/kg in women, one half in men [15], assuming an 81% bioavailability [16] and a homogeneous distribution, then the quantity of dexamethasone reaching the anterior chamber (161.2 μl) after systemic administration would theoretically be about 0.011 nMoles, i.e. the same order of magnitude as the dexamethasone amount measured in the anterior chamber in our study.…”

Section: Discussionmentioning

confidence: 99%

Aqueous humour concentrations after topical apPlication of combinEd levofloxacin-dexamethasone eye dRops and of its single components: a randoMised, assEssor-blinded, parallel-group study in patients undergoing cataract surgery: the iPERME study

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Posarelli

Romano

et al. 2020

Eur J Clin Pharmacol

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Purpose To evaluate the penetration of levofloxacin and dexamethasone sodium phosphate into the aqueous humour (AH) after administration in combination and as single molecules. Evaluation of the penetration of those agents in the site of action and their pharmacodynamic potential activity in view of the intended clinical use after cataract surgery. Methods Randomised, assessor-blinded, parallel-group. Patients scheduled for cataract surgery were assigned in a 1:1:1 ratio to: levofloxacin + dexamethasone sodium phosphate (L-DSP), Levofloxacin (L) or Dexamethasone sodium phosphate (DSP) eye drops. Either test or reference drugs were instilled in the cul-de-sac twice, 90 and 60 min before paracentesis. Results A total of 125 patients completed the study. Fraction of dose absorbed in the anterior chamber was 3.8-4.2 • 10 −4 for levofloxacin and 0.3-0.4 • 10 −4 for dexamethasone, respectively. No notable differences in concentration of levofloxacin were found between L-DSP arm (1.970 nmol/ml) and L arm (2.151 nmol/ml). The concentrations of levofloxacin were well above the MICs for the most frequent Gram-positive and Gram-negative eye pathogens. Dexamethasone concentrations were slightly lower in L-DSP arm (0.030 nmol/ml) than in DSP arm (0.042 nmol/ml), but still in the pharmacodynamically active range in the site of action. The difference was not clinically relevant. DSP was not detected in any HA sample, suggesting its full hydrolysis to free dexamethasone. Conclusion Our results confirm that no interaction is evident on the corneal penetration of levofloxacin and dexamethasone which reach pharmacologically active concentrations when instilled as fixed combination eye drops to patients undergoing cataract surgery. Trial registration ClinicalTrials.gov Identifier: NCT03740659

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“…Once drugs are consumed, they are gradually eliminated or metabolized by a specific hepatic microsomal enzyme system [5–7]. To measure the precise amount of time that a drug is effective and control the proper drug dosage, a specific drug parameter, the drug half-life, serves to standardize the use of drugs and avoid side effects [8, 9]. …”

Section: Introductionmentioning

confidence: 99%

The Use of Gene Ontology Term and KEGG Pathway Enrichment for Analysis of Drug Half-Life

et al. 2016

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A drug’s biological half-life is defined as the time required for the human body to metabolize or eliminate 50% of the initial drug dosage. Correctly measuring the half-life of a given drug is helpful for the safe and accurate usage of the drug. In this study, we investigated which gene ontology (GO) terms and biological pathways were highly related to the determination of drug half-life. The investigated drugs, with known half-lives, were analyzed based on their enrichment scores for associated GO terms and KEGG pathways. These scores indicate which GO terms or KEGG pathways the drug targets. The feature selection method, minimum redundancy maximum relevance, was used to analyze these GO terms and KEGG pathways and to identify important GO terms and pathways, such as sodium-independent organic anion transmembrane transporter activity (GO:0015347), monoamine transmembrane transporter activity (GO:0008504), negative regulation of synaptic transmission (GO:0050805), neuroactive ligand-receptor interaction (hsa04080), serotonergic synapse (hsa04726), and linoleic acid metabolism (hsa00591), among others. This analysis confirmed our results and may show evidence for a new method in studying drug half-lives and building effective computational methods for the prediction of drug half-lives.

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Prediction of Drug Terminal Half-Life and Terminal Volume of Distribution After Intravenous Dosing Based on Drug Clearance, Steady-State Volume of Distribution, and Physiological Parameters of the Body

Cited by 13 publications

References 53 publications

On the Accuracy of a One-Compartment Approach for Determination of Drug Terminal Half-Life

On the Accuracy of a One-Compartment Approach for Determination of Drug Terminal Half-Life

Aqueous humour concentrations after topical apPlication of combinEd levofloxacin-dexamethasone eye dRops and of its single components: a randoMised, assEssor-blinded, parallel-group study in patients undergoing cataract surgery: the iPERME study

The Use of Gene Ontology Term and KEGG Pathway Enrichment for Analysis of Drug Half-Life

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