Excipient pharmacokinetics and profiling

Loftsson, Þorsteinn

doi:10.1016/j.ijpharm.2015.01.022

Cited by 31 publications

(17 citation statements)

References 52 publications

(32 reference statements)

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“…Protein binding also decreases the glomerular filtration rate of drugs as well as their enzymatic degradation; both of which will result in increased t ½ (i.e. decrease the observed elimination rate constant [k] ) [14]. Drug total body clearance (Cl T ) is the product of the volume of distribution and the first‐order rate constant for drug elimination (Cl T = V D ·k).…”

Section: Parenteral Administrationmentioning

confidence: 99%

“…[12] After parenteral administration, CDs, such as HPβCD, SBEβCD and sugammadex are rapidly excreted intact from the body in urine via glomerular filtration. [13,14] For example, HPβCD has a small volume of distribution (VD ≈ 0.2 l/kg) and a short half-life (t 1 ⁄2 ≈ 1.7 h in humans with normal kidney function), and is mainly (approximately 97%) excreted unchanged in urine after parenteral administration. [10,15,16] This small VD and short t 1 ⁄2 indicate that HPβCD is mainly located in the blood plasma after parenteral administration and cleared from the blood at a rate that is close to the glomerular filtration rate without tubular reabsorption.…”

Section: Excretionmentioning

confidence: 99%

“…decrease the observed elimination rate constant [k] ). [14] Drug total body clearance (ClT) is the product of the volume of distribution and the first-order rate constant for drug elimination (ClT = VD·k). Plasma proteins and CDs are both able to form complexes with drug molecules, where bound drug molecules are in equilibrium with free molecules in an aqueous environment.…”

Section: Parenteral Administration Of Drug/cd Complexesmentioning

confidence: 99%

“…It is known that the degradation rate of CDs in the GI tract can be hampered by inclusion complex formation [12]. After parenteral administration, CDs, such as HPβCD, SBEβCD and sugammadex are rapidly excreted intact from the body in urine via glomerular filtration [13,14]. For example, HPβCD has a small volume of distribution (V D ≈ 0.2 l/kg) and a short half‐life (t ½ ≈ 1.7 h in humans with normal kidney function), and is mainly (approximately 97%) excreted unchanged in urine after parenteral administration [10,15,16].…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetics of cyclodextrins and drugs after oral and parenteral administration of drug/cyclodextrin complexes

Loftsson

Moya‐Ortega

Alvarez‐Lorenzo

2015

Journal of Pharmacy and Pharmacology

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Objectives The objective of the present study was to shed some light on pharmacokinetics of cyclodextrins (CDs) and drugs after oral and parenteral administration of inclusion complexes. Key findings The complex binding constant in water can predict pharmacokinetics after parenteral administration, but it has to be considered in the context of the physiological environment, where plasma proteins compete with CDs for drug binding. Neither drug/CD nor drug/protein complexes can extravasate, but differently from proteins, CDs are readily cleared through glomerular filtration. In such intricate interrelationships, for complexes with low-to-mid binding constant, binding of drug to plasma proteins will mainly dictate the pharmacokinetics. Oppositely, for drugs showing large CD complex binding constant and low protein binding, significant decrease in distribution volume and enhanced excretion of unmetabolized drug are observed; thus, relevant changes in bioavailability can be predicted. In the case of oral administration, volume for dilution/dissolution of the complexes is relatively low and hence excess CD can hamper drug absorption from the gastrointestinal (GI) tract. Summary CDs are well-established multipurpose excipients for overcoming organoleptic and biopharmaceutical deficiencies of a variety of drugs. Balances between free and complexed drug in the GI tract and between drug-CD binding and drug-protein binding in plasma seem to play a relevant role in drug pharmacokinetics.

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Section: Parenteral Administrationmentioning

confidence: 99%

Section: Excretionmentioning

confidence: 99%

Section: Parenteral Administration Of Drug/cd Complexesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetics of cyclodextrins and drugs after oral and parenteral administration of drug/cyclodextrin complexes

Loftsson

Moya‐Ortega

Alvarez‐Lorenzo

2015

Journal of Pharmacy and Pharmacology

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“…Moreover, excipients perform multiple functions, besides completing the formulation volume, such as improving bioavailability, administration and acceptance of the treatment by the patient (Loftsson, 2015;Narayan, 2011;Wening and Breitkreutz, 2011). Another fundamental characteristic of excipients is their pharmacological and toxicological inactivity that allows them to be used at high doses (Abrantes et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

EXCI-CEST: Exploiting pharmaceutical excipients as MRI-CEST contrast agents for tumor imaging

Longo

Moustaghfir

Zerbo

et al. 2017

International Journal of Pharmaceutics

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Chemical Exchange Saturation Transfer (CEST) approach is a novel tool within magnetic resonance imaging (MRI) that allows visualization of molecules possessing exchangeable protons with water. Many molecules, employed as excipients for the formulation of finished drug products, are endowed with hydroxyl, amine or amide protons, thus can be exploitable as MRI-CEST contrast agents. Their high safety profiles allow them to be injected at very high doses. Here we investigated the MRI-CEST properties of several excipients (ascorbic acid, sucrose, N-acetyl-d-glucosamine, meglumine and 2-pyrrolidone) and tested them as tumor-detecting agents in two different murine tumor models (breast and melanoma cancers). All the investigated molecules showed remarkable CEST contrast upon i.v. administration in the range 1-3ppm according to the type of mobile proton groups. A marked increase of CEST contrast was observed in tumor regions up to 30min post injection. The combination of marked tumor contrast enhancement and lack of toxicity make these molecules potential candidates for the diagnosis of tumors within the MRI-CEST approach.

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Applications of Freeze‐drying in Pharmaceuticals, Biopharmaceuticals, and Foods

2018

Ice Templating and Freeze‐Drying for Porous Materials and Their Applications

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Excipient pharmacokinetics and profiling

Cited by 31 publications

References 52 publications

Pharmacokinetics of cyclodextrins and drugs after oral and parenteral administration of drug/cyclodextrin complexes

Pharmacokinetics of cyclodextrins and drugs after oral and parenteral administration of drug/cyclodextrin complexes

EXCI-CEST: Exploiting pharmaceutical excipients as MRI-CEST contrast agents for tumor imaging

Applications of Freeze‐drying in Pharmaceuticals, Biopharmaceuticals, and Foods

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