{"id":{"repo_id":"vcu","oai_identifier":"oai:scholarscompass.vcu.edu:etd-2014"},"canonical_url":"https://search.dev.ndltd.org/etd/vcu/oai:scholarscompass.vcu.edu:etd-2014","repository":{"repo_id":"vcu","name":"Virginia Commonwealth University","base_url":"https://scholarscompass.vcu.edu/do/oai/"},"display":{"title":"Interspecies Pharmacokinetic Scaling and Metabolism of Alcohols and Glycols","abstract":"Background: Despite the numerous pharmaceutical applications of alcohols andglycols, the interspecies differences with respect to their pharmacokinetics (PK) arepoorly understood. The aim of this research was to use in-vivo and in-vitro approaches to compare and model the PK characteristics across various species.Methods: Appropriate published in-vivo studies (in different species) foralcohols and glycols were carefully selected. PK analysis was performed using (a) noncompartmental analysis and (b) compartmental modeling to estimate relevant dose-independent PK parameters. Next, six alcohols (methanol, ethanol, 1 -propanol, 1 -butanol, 1-hexanol, and 1-octanol), two glycols (ethylene glycol and propylene glycol)and one secondary alcohol (2-propanol) were examined as in-vitro substrates for equine ADH using a UV spectrophotometric assay to evaluate the effect of molecular structure. Furthermore, in-vitro metabolism of ethanol and propylene glycol was also characterized in hepatic cytosolic fractions from rat, rabbit, dog and human and in-vitro in-vivo correlation for the hepatic disposition parameters was assessed. Finally, allometric scaling relationships for ethanol and propylene glycol PK parameters (in-vivo and in-vitro) were developed and validated.Results: Alcohols and glycols exhibited nonlinear PK due to saturable hepaticmetabolism in all species. The reported in-vivo data were well described by oneltwo compartment PK models with parallel saturable metabolism and first-order renalexcretion. In-vitro equine ADH experiments revealed differences in affinity andturnover between the substrates: Enzyme affinity (1/Km) and in-vitro intrinsic clearance (CLintin-vitro) correlated positively with logP values; glycols showed lower CLintin-vitro values than straight-chain alcohols. In-vitro hepatic cytosol studies yielded acceptable in-vivo predictions for the metabolic clearance (CLmet) of ethanol and propylene glycol in the rat, dog and human, but not the rabbit. Vdss, Vmax, CLintin-vitro, CLmet scaled allometrically across species with similar powers for both ethanol and propylene glycol, and good agreement between in-vivo and in-vitro scaling was noted. The allometric scaling models gave excellent predictions when externally validated against in-vivo concentration-time data. Conclusions: The present research demonstrates .the successful application of amodeling-based approach to elucidate interspecies relationships for alcohols andglycols, compounds which exhibit nonlinear PK and mainly low hepatic extractionbehavior. The in-vitro experimental systems have been used successfully forcharacterizing alcohol/glycol metabolism and predicting in-vivo disposition.","abstract_html":"Background: Despite the numerous pharmaceutical applications of alcohols andglycols, the interspecies differences with respect to their pharmacokinetics (PK) arepoorly understood. The aim of this research was to use in-vivo and in-vitro approaches to compare and model the PK characteristics across various species.Methods: Appropriate published in-vivo studies (in different species) foralcohols and glycols were carefully selected. PK analysis was performed using (a) noncompartmental analysis and (b) compartmental modeling to estimate relevant dose-independent PK parameters. Next, six alcohols (methanol, ethanol, 1 -propanol, 1 -butanol, 1-hexanol, and 1-octanol), two glycols (ethylene glycol and propylene glycol)and one secondary alcohol (2-propanol) were examined as in-vitro substrates for equine ADH using a UV spectrophotometric assay to evaluate the effect of molecular structure. Furthermore, in-vitro metabolism of ethanol and propylene glycol was also characterized in hepatic cytosolic fractions from rat, rabbit, dog and human and in-vitro in-vivo correlation for the hepatic disposition parameters was assessed. Finally, allometric scaling relationships for ethanol and propylene glycol PK parameters (in-vivo and in-vitro) were developed and validated.Results: Alcohols and glycols exhibited nonlinear PK due to saturable hepaticmetabolism in all species. The reported in-vivo data were well described by oneltwo compartment PK models with parallel saturable metabolism and first-order renalexcretion. In-vitro equine ADH experiments revealed differences in affinity andturnover between the substrates: Enzyme affinity (1/Km) and in-vitro intrinsic clearance (CLintin-vitro) correlated positively with logP values; glycols showed lower CLintin-vitro values than straight-chain alcohols. In-vitro hepatic cytosol studies yielded acceptable in-vivo predictions for the metabolic clearance (CLmet) of ethanol and propylene glycol in the rat, dog and human, but not the rabbit. Vdss, Vmax, CLintin-vitro, CLmet scaled allometrically across species with similar powers for both ethanol and propylene glycol, and good agreement between in-vivo and in-vitro scaling was noted. The allometric scaling models gave excellent predictions when externally validated against in-vivo concentration-time data. Conclusions: The present research demonstrates .the successful application of amodeling-based approach to elucidate interspecies relationships for alcohols andglycols, compounds which exhibit nonlinear PK and mainly low hepatic extractionbehavior. The in-vitro experimental systems have been used successfully forcharacterizing alcohol/glycol metabolism and predicting in-vivo disposition.","abstract_has_math":false,"creators":["Gupta, Pankaj"],"institution":null,"degree_name":"Doctor of Philosophy","degree_level":"Dissertation","degree_discipline":"Pharmaceutics","degree_department":null,"school":null,"contributors":["Dr. Jürgen Venitz"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2006,"date_issued":"2006-01-01T08:00:00Z","date_published":"2006-01-01T08:00:00Z","updated_at":"2026-07-24T05:54:47Z","subjects":["ethanol","propylene","hydrophobic drugs","Medicine and Health Sciences","Pharmacy and Pharmaceutical Sciences"],"languages":[],"rights":["© The Author"],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["https://scholarscompass.vcu.edu/etd/1015"],"render_values":[{"text":"https://scholarscompass.vcu.edu/etd/1015","href":"https://scholarscompass.vcu.edu/etd/1015","code":true}]}]},"links":{"outbound_url":"https://doi.org/10.25772/EZB2-PX23","outbound_label":"DOI","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Dr. Jürgen Venitz"]},{"key":"dc:creator","label":"Author","values":["Gupta, Pankaj"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2014-07-09T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Pharmaceutics"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["ethanol","propylene","hydrophobic drugs","Medicine and Health Sciences","Pharmacy and Pharmaceutical Sciences"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["© The Author"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://doi.org/10.25772/EZB2-PX23","https://scholarscompass.vcu.edu/etd/1015"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Background: Despite the numerous pharmaceutical applications of alcohols andglycols, the interspecies differences with respect to their pharmacokinetics (PK) arepoorly understood. The aim of this research was to use in-vivo and in-vitro approaches to compare and model the PK characteristics across various species.Methods: Appropriate published in-vivo studies (in different species) foralcohols and glycols were carefully selected. PK analysis was performed using (a) noncompartmental analysis and (b) compartmental modeling to estimate relevant dose-independent PK parameters. Next, six alcohols (methanol, ethanol, 1 -propanol, 1 -butanol, 1-hexanol, and 1-octanol), two glycols (ethylene glycol and propylene glycol)and one secondary alcohol (2-propanol) were examined as in-vitro substrates for equine ADH using a UV spectrophotometric assay to evaluate the effect of molecular structure. Furthermore, in-vitro metabolism of ethanol and propylene glycol was also characterized in hepatic cytosolic fractions from rat, rabbit, dog and human and in-vitro in-vivo correlation for the hepatic disposition parameters was assessed. Finally, allometric scaling relationships for ethanol and propylene glycol PK parameters (in-vivo and in-vitro) were developed and validated.Results: Alcohols and glycols exhibited nonlinear PK due to saturable hepaticmetabolism in all species. The reported in-vivo data were well described by oneltwo compartment PK models with parallel saturable metabolism and first-order renalexcretion. In-vitro equine ADH experiments revealed differences in affinity andturnover between the substrates: Enzyme affinity (1/Km) and in-vitro intrinsic clearance (CLintin-vitro) correlated positively with logP values; glycols showed lower CLintin-vitro values than straight-chain alcohols. In-vitro hepatic cytosol studies yielded acceptable in-vivo predictions for the metabolic clearance (CLmet) of ethanol and propylene glycol in the rat, dog and human, but not the rabbit. Vdss, Vmax, CLintin-vitro, CLmet scaled allometrically across species with similar powers for both ethanol and propylene glycol, and good agreement between in-vivo and in-vitro scaling was noted. The allometric scaling models gave excellent predictions when externally validated against in-vivo concentration-time data. Conclusions: The present research demonstrates .the successful application of amodeling-based approach to elucidate interspecies relationships for alcohols andglycols, compounds which exhibit nonlinear PK and mainly low hepatic extractionbehavior. The in-vitro experimental systems have been used successfully forcharacterizing alcohol/glycol metabolism and predicting in-vivo disposition."]},{"key":"dc:title","label":"Title","values":["Interspecies Pharmacokinetic Scaling and Metabolism of Alcohols and Glycols"]}]}],"canonical_facts":{"dc:contributor":["Dr. Jürgen Venitz"],"dc:creator":["Gupta, Pankaj"],"dc:date.available":["2014-07-09T07:00:00Z"],"dc:description.abstract":["Background: Despite the numerous pharmaceutical applications of alcohols andglycols, the interspecies differences with respect to their pharmacokinetics (PK) arepoorly understood. The aim of this research was to use in-vivo and in-vitro approaches to compare and model the PK characteristics across various species.Methods: Appropriate published in-vivo studies (in different species) foralcohols and glycols were carefully selected. PK analysis was performed using (a) noncompartmental analysis and (b) compartmental modeling to estimate relevant dose-independent PK parameters. Next, six alcohols (methanol, ethanol, 1 -propanol, 1 -butanol, 1-hexanol, and 1-octanol), two glycols (ethylene glycol and propylene glycol)and one secondary alcohol (2-propanol) were examined as in-vitro substrates for equine ADH using a UV spectrophotometric assay to evaluate the effect of molecular structure. Furthermore, in-vitro metabolism of ethanol and propylene glycol was also characterized in hepatic cytosolic fractions from rat, rabbit, dog and human and in-vitro in-vivo correlation for the hepatic disposition parameters was assessed. Finally, allometric scaling relationships for ethanol and propylene glycol PK parameters (in-vivo and in-vitro) were developed and validated.Results: Alcohols and glycols exhibited nonlinear PK due to saturable hepaticmetabolism in all species. The reported in-vivo data were well described by oneltwo compartment PK models with parallel saturable metabolism and first-order renalexcretion. In-vitro equine ADH experiments revealed differences in affinity andturnover between the substrates: Enzyme affinity (1/Km) and in-vitro intrinsic clearance (CLintin-vitro) correlated positively with logP values; glycols showed lower CLintin-vitro values than straight-chain alcohols. In-vitro hepatic cytosol studies yielded acceptable in-vivo predictions for the metabolic clearance (CLmet) of ethanol and propylene glycol in the rat, dog and human, but not the rabbit. Vdss, Vmax, CLintin-vitro, CLmet scaled allometrically across species with similar powers for both ethanol and propylene glycol, and good agreement between in-vivo and in-vitro scaling was noted. The allometric scaling models gave excellent predictions when externally validated against in-vivo concentration-time data. Conclusions: The present research demonstrates .the successful application of amodeling-based approach to elucidate interspecies relationships for alcohols andglycols, compounds which exhibit nonlinear PK and mainly low hepatic extractionbehavior. The in-vitro experimental systems have been used successfully forcharacterizing alcohol/glycol metabolism and predicting in-vivo disposition."],"dc:identifier":["https://doi.org/10.25772/EZB2-PX23","https://scholarscompass.vcu.edu/etd/1015"],"dc:rights":["© The Author"],"dc:subject":["ethanol","propylene","hydrophobic drugs","Medicine and Health Sciences","Pharmacy and Pharmaceutical Sciences"],"dc:title":["Interspecies Pharmacokinetic Scaling and Metabolism of Alcohols and Glycols"],"thesis:degree_discipline":["Pharmaceutics"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy"]},"updated_at":"2026-07-24T05:54:47Z"}