Disposition of 8-methyl-8-azabicyclo[3,2,1]octan-3-yl 3,5-dichlorobenzoate, a potent 5-hydroxytryptamine antagonist, and two metabolites in dogs and monkeys.

The disposition of 8-methyl-8-azabicyclo[3,2,1]octan-3-yl 3,5-dichlorobenzoate (MDL 72,222; 1), a potent 5-hydroxytryptamine antagonist, and its N-demethylated and N-oxide metabolites was studied in dogs and monkeys. After single, intravenous doses of 1 at 5 mg/kg, the mean terminal half-lives of 1 in plasma were 2.6 h in the dog and 3.8 h in the monkey. The mean half-life of the N-demethylated metabolite in dogs (approximately 20 h) was very similar to that in monkeys. However, the mean half-life of the N-oxide metabolite in dogs (10.8 h) was different from that in monkeys (3.9 h). The steady-state volume of distribution of 1 was 16 L/kg in dogs and 8.9 L/kg in monkeys. Examination of the mean residence times revealed that 1, in both species, and the N-oxide metabolite, in dogs, distributed to the peripheral tissue, whereas the distribution of the N-demethylated metabolite in both species and the N-oxide metabolite in monkeys was limited mainly to the systemic circulation. Compound 1 was metabolized extensively in both species. In dogs, 0.7, 2.5 and 40.6% of the administered dose were excreted in 0-120-h urine samples as 1 and its N-demethylated and N-oxide metabolites, respectively. In monkeys, however, the corresponding percentages were 0.8, 0.7, and 1.8%. Most of the administered dose in monkeys was excreted in urine as 3,5-dichlorobenzoic acid and its glycine conjugate.     

Gas Chromatographic–Mass Spectrometric (GC-MS) Determination of MDL 72,222 and Four Metabolites in Monkey Plasma

MDL 72,222, a potent serotonin antagonist, is being developed for use as an antiemetic drug in cancer chemotherapy. An assay method has been developed for the determination of MDL 72,222 and four metabolites: N-desmethyl-MDL 72,222 (1), 3,5-dichlorobenzoic acid (2), glycine conjugate of 2 (3), and MDL 72,222-N-oxide (4). The method involves liquid–liquid extractions, derivatization with trifluoroacetic anhydride for metabolite 1, methylation with diazomethane for metabolites 2 and 3, reduction with titanous chloride for 4, and detection of each analyte by GC-MS. In this method d ₃-MDL 72,222, a 3-methyl-5-chlorobenzoate analogue of 1 (5), and 3,4-dichlorobenzoate analogues of 2–4 (6–8) are used as internal standards for the determination of MDL 72,222 and metabolites 1, 2, 3, and 4, respectively. The method is suitable for quantification of MDL 72,222 and the metabolites 1-4 over a concentration range of 1–150, 0.5–75, 1–150, 0.5–75, and 1–150 ng/ml, respectively. The intraday precision and accuracy values are within 10% RSD and 92–110%, respectively. The interday precision and accuracy values are within 14% RSD and 87.6–116%, respectively. The method is specific and sensitive for the analysis of MDL 72,222 and four metabolites in monkey plasma. The assay method has been utilized in analyzing pharmacokinetic study samples.     

Species differences in the metabolism of suprofen in laboratory animals and man

The metabolism of the oral anti-inflammatory agent suprofen (S), 2-4-(2-thienylcarbonyl)phenyl)propionic acid, has been studied in mice, rats, guinea pigs, dogs, monkeys, and human volunteers. The major metabolites of S in the serum, urine, and feces of these species were determined by GC/MS and HPLC techniques. The metabolic pathways of S in these species involved reduction of the ketone group to an alcohol (S-OH), hydroxylation of the thiophene ring (T-OH), elimination of the thiophene ring to a dicarboxylic acid (S-COOH), and conjugation with glucuronic acid or taurine. In 72-hr urine and feces of these species after po dosing of 1.6 to 2 mg/kg of S, S and these metabolites accounted for 46 to 92% of the dose and were mainly excreted in the urine. S was present as a major product (excreted mainly in conjugated form) in all species. S-OH was a major component in guinea pig and dog but a minor one in other species. T-OH was identified as a major metabolite in monkey, rat, mouse, and man, but a minor one in guinea pig, and it was absent in the dog. S-COOH was present as the minor metabolite in mouse and rat, and present at trace levels in dog, monkey, and man. Conjugation of the propionic acid functionality with taurine was observed only in the dog; in the other species, conjugation with glucuronic acid was extensive. Absorption parameters of S in the rat and monkey were similar to those in man; however, other species were very different from man.     

Comparison of celecoxib metabolism and excretion in mouse,rabbit, dog,cynomolgus monkey and rhesus monkey

1. The metabolism and excretion of celecoxib, a specific cyclooxygenase 2 (COX-2) inhibitor, was investigated in mouse, rabbit,the EM(extensive) and PM(poor metabolizer) dog, and rhesus and cynomolgus monkey. 2. Some sex and species differences were evident in the disposition of celecoxib. After intravenous (i.v.) administration of [¹⁴C]celecoxib, the major route of excretion of radioactivity in all species studied was via the faeces: EM dog (80.0%), PM dog (83.4%), cynomolgus monkey (63.5%), rhesus monkey (83.1%). After oral administration, faeces were the primary route of excretion in rabbit (72.2%) and the male mouse (71.1%), with the remainder of the dose excreted in the urine. After oral administration of [¹⁴C]celecoxib to the female mouse, radioactivity was eliminated equally in urine (45.7%) and faeces (46.7%). 3. Biotransformation of celecoxib occurs primarily by oxidation of the aromatic methyl group to form a hydroxymethyl metabolite, which is further oxidized to the carboxylic acid analogue. 4. An additional phase I metabolite (phenyl ring hydroxylation) and a glucuronide conjugate of the carboxylic acid metabolite was produced by rabbit. 5. The major excretion product in urine and faeces of mouse, rabbit, dog and monkey was the carboxylic acid metabolite of celecoxib.     

Comparison of celecoxib metabolism and excretion in mouse, rabbit, dog, cynomolgus monkey and rhesus monkey

1. The metabolism and excretion of celecoxib, a specific cyclooxygenase 2 (COX-2) inhibitor, was investigated in mouse, rabbit, the EM (extensive) and PM (poor metabolizer) dog, and rhesus and cynomolgus monkey. 2. Some sex and species differences were evident in the disposition of celecoxib. After intravenous (i.v.) administration of [14C]celecoxib, the major route of excretion of radioactivity in all species studied was via the faeces: EM dog (80.0%), PM dog (83.4%), cynomolgus monkey (63.5%), rhesus monkey (83.1%). After oral administration, faeces were the primary route of excretion in rabbit (72.2%) and the male mouse (71.1%), with the remainder of the dose excreted in the urine. After oral administration of [14C]celecoxib to the female mouse, radioactivity was eliminated equally in urine (45.7%) and faeces (46.7%). 3. Biotransformation of celecoxib occurs primarily by oxidation of the aromatic methyl group to form a hydroxymethyl metabolite, which is further oxidized to the carboxylic acid analogue. 4. An additional phase I metabolite (phenyl ring hydroxylation) and a glucuronide conjugate of the carboxylic acid metabolite was produced by rabbit. 5. The major excretion product in urine and faeces of mouse, rabbit, dog and monkey was the carboxylic acid metabolite of celecoxib.     

Excretion and metabolism of recainam, a new anti-arrhythmic drug, in laboratory animals and humans

The metabolic disposition of recainam, an antiarrhythmic drug, was compared in mice, rats, dogs, rhesus monkeys, and humans. Following oral administration of [14C]recainam-HCl, radioactivity was excreted predominantly in the urine of all species except the rat. Metabolite profiles were determined in excreta by HPLC comparisons with synthetic standards. In rodents and rhesus monkeys, urinary excretion of unchanged recainam accounted for 23-36% of the iv dose and 3-7% of the oral dose. Aside from quantitative differences attributable to presystemic biotransformation, metabolite profiles were qualitatively similar following oral or iv administration to rodents and rhesus monkeys. Recainam was extensively metabolized in all species except humans. In human subjects, 84% of the urinary radioactivity corresponded to parent drug. The major metabolites in mouse and rat urine and rat feces were m- and p-hydroxyrecainam. Desisopropylrecainam and dimethylphenylaminocarboxylamino propionic acid were the predominant metabolites in dog and rhesus monkey urine. Small amounts of desisopropylrecainam and p-hydroxyrecainam were excreted in human urine. Selective enzymatic hydrolysis revealed that the hydroxylated metabolites were conjugated to varying degrees among species. Conjugated metabolites were not present in rat urine or feces, while conjugates were detected in mouse, dog, and monkey urine. Structural confirmation of the dog urinary metabolites was accomplished by mass spectral analysis. The low extent of metabolism of recainam in humans suggests that there will not be wide variations between dose and plasma concentrations.     

Metabolism of actisomide in the dog, monkey and man: a novel rearrangement of N-dealkylated metabolites.

The metabolism of actisomide, a novel antiarrhythmic agent, was studied in the dog, monkey and man and was found to be more extensive in the monkey than in the dog or man. The major metabolites identified were a piperidinyl hydroxylated metabolite, the mono-N-dealkylated, cyclized and piperidine hydroxylated metabolite, and the cyclized and mono-N-dealkylated metabolite. Excretion of the parent drug was higher in urine than in feces in the dog, but in the monkey and man, urinary and fecal excretion of actisomide was similar. In all species the metabolites were primarily excreted in feces.     

Metabolism of Femoxetine

Abstract: The metabolism of femoxetine, a serotonin uptake inhibitor, has been investigated in rats, dogs, monkeys, and human subjects using two ¹⁴C-femoxetine compounds with labelling in different positions. The metabolic pathways were oxidation (and glucuronidation) and demethylation, both reactions most probably taking place in the liver. Nearly all femoxetine was metabolised, and the same metabolites were found in urine from all four species. Only a small percentage of the radioactivity excreted in the urine was not identified. Rat and dog excreted more N-oxide than monkey and man, while most of the radioactivity (60–100%) in these two species was excreted as two hydroxy metabolites. The metabolic pattern in monkey and man was very similar. About 50% was excreted in these two species as one metabolite, formed by demethylation of a methoxy group. A demethylation of a N-CH₃ group formed an active metabolite, norfemoxetine. The excretion of this metabolite in urine from man varied from 0 to 18% of the dose between individuals. Most of the radioactivity was excreted with the faeces in rat and dog, while monkey and man excreted most of the radioactivity in urine. This difference in excretion route might be explained by the difference in the metabolic pattern. No dose dependency was observed in any of the three animal species investigated.     

Urinary metabolites of a novel quinoxaline non-nucleoside reverse transcriptase inhibitor in dog, cynomolgus monkey and mini-pig.

1. The metabolism of (S)-2-ethyl-7-fluoro-3-oxo-3,4-dihydro-2H-quinoxalinecarboxylic acid isopropylester (GW420867X) has been investigated following oral administration to dog, cynomolgus monkey and mini-pig. 2. The urinary metabolites were isolated and characterized using semi-preparative HPLC, NMR and LC-MS/MS. The relative proportions of fluorine-containing metabolites were determined for each species by 19F-NMR signal integration. 3. The metabolite profiles for each species were similar, although the proportion of individual components varied, suggesting that similar metabolic pathways are involved in the biotransformation of GW420867X in the species studied. 4. The urinary metabolites indicated that the major routes of biotransformation included hydroxylation and subsequent glucuronic acid conjugation on the aromatic ring, and on the ethyl and isopropyl side chains. A component was observed in mini-pig urine that corresponded to hydroxylation and glucuronidation accompanied by loss of the fluorine atom.     

Disposition and metabolism of almotriptan in rats,dogs and monkeys

Almotriptan is a new highly potent selective 5-HT_1B/1D receptor agonist developed for the treatment of migraine, and the disposition of almotriptan in different animal species is now addressed in the current study. Almotriptan was well absorbed in rats (69.1%) and dogs (100%) following oral treatment. The absolute bioavailability was variable reflecting different degrees of absorption and first-pass metabolism (18.7–79.6%). The elimination half-life was short and ranged between 0.7 and 3?h. The main route of elimination of almotriptan was urine with 75.6% and 80.4% of the dose recovered over a 168-h period in rats and dogs, respectively. The γ-aminobutyric acid metabolite formed by oxidation of the pyrrolidine ring was the main metabolite found in urine, faeces, bile, and plasma of rats and in monkey urine. By contrast, the unchanged drug, the indole acetic acid metabolite formed by oxidative deamination of the dimethylaminoethyl group, and the N-oxide metabolite were the main metabolites in dog.     

Disposition and metabolism of almotriptan in rats, dogs and monkeys

Almotriptan is a new highly potent selective 5-HT1B/1D receptor agonist developed for the treatment of migraine, and the disposition of almotriptan in different animal species is now addressed in the current study. Almotriptan was well absorbed in rats (69.1%) and dogs (100%) following oral treatment. The absolute bioavailability was variable reflecting different degrees of absorption and first-pass metabolism (18.7-79.6%). The elimination half-life was short and ranged between 0.7 and 3 h. The main route of elimination of almotriptan was urine with 75.6% and 80.4% of the dose recovered over a 168-h period in rats and dogs, respectively. The gamma-aminobutyric acid metabolite formed by oxidation of the pyrrolidine ring was the main metabolite found in urine, faeces, bile, and plasma of rats and in monkey urine. By contrast, the unchanged drug, the indole acetic acid metabolite formed by oxidative deamination of the dimethylaminoethyl group, and the N-oxide metabolite were the main metabolites in dog.     

Metabolism of 14C-estazolam in dogs and humans

14C-Estazolam (2 mg) administered orally to dogs and human subjects was rapidly and completely absorbed with peak plasma levels occurring within one hour. In humans, plasma levels peaked at 103 +/- 18 ng/ml and declined monoexponentially with a half-life of 14 h. The mean concn. of estazolam in dog plasma at 0.5 h was 186 ng/ml. Six metabolites were found in dog plasma at 0.5 and 8 h, whereas only two metabolites were detected in human plasma up to 18 h. Metabolites common to both species were 1-oxo-estazolam (I) and 4-hydroxy-estazolam (IV). Major metabolites in dog and human plasma were free and conjugated 4-hydroxy-estazolam; the concn. were higher in dogs. After five days, 79% and 87% of the administered radioactivity was excreted in dog and human urine, respectively. Faecal excretion accounted for 19% of the dose in dog and 4% in man. Eleven metabolites were found in the 0-72 h urine of dogs and humans; less than 4% dose was excreted unchanged. Four metabolites were identified as: 1-oxo-estazolam (I), 4'-hydroxy-estazolam (II), 4-hydroxy-estazolam (IV) and the benzophenone (VII), as free metabolites and glucuronides. The major metabolite in dog urine was 4-hydroxy-estazolam (20% of the dose), while the predominant metabolite in human urine (17%) has not been identified, but is likely to be a metabolite of 4-hydroxy-estazolam. The metabolism of estazolam is similar in dog and man.     

Metabolism and disposition of sulfinalol in laboratory animals

Peak levels of radioactivity in blood occurred 1.0 hr after oral administration of 3H-sulfinalol hydrochloride to rats, dogs, and monkeys. The plasma decay curve for intact sulfinalol in the dog was biphasic, with apparent first-order half-lives of 0.55 and 6.2 hr. Rats excreted 42.5% of the dose in the urine and 31.8% in the feces after 24 hr. Urinary and fecal recovery were 53.8% and 41.2%, respectively, after 10 days for dogs and 57.8% and 38.0%, respectively, after 9 days for monkeys. Free sulfinalol (11.8% of the dose) was the major component in dog feces with lesser amounts of the sulfide and sulfone metabolites, also in the unconjugated form. All metabolites in dog urine were conjugated with glucuronic acid, with sulfinalol (28.5%) and desmethylsulfinalol (8.5%) representing the major constituents, whereas the sulfone and sulfide metabolites were minor ones. Monkey feces contained primarily unconjugated forms of the desmethyl sulfide metabolite (17.0%) and sulfinalol (7.5%); lesser amounts of desmethylsulfinalol and the sulfone metabolite were present. Desmethylsulfinalol (8.7%) and its sulfate (7.0%) and glucuronide (4.0%) conjugates were the major urinary metabolites in the monkey; sulfinalol (1.4%), its glucuronide conjugate (5.1%), the desmethyl sulfide metabolite (and its sulfate conjugate), and the sulfone metabolite were also present.     

Metabolic hydroxylation of the thiophene ring: Isolation of 5-hydroxy-tienilic acid as the major urinary metabolite of tienilic acid in man and rat

The metabolism of tienilic acid, a drug containing a thiophene ring, was reinvestigated in man, rat and dog. The major urinary metabolite in man and rat was isolated and completely characterized by comparison with a synthetic compound. This metabolite derives from the hydroxylation of the thiophene ring of tienilic acid in position 5. Its isomers, 3- and 4-hydroxy-tienilic acids, were synthetized but could be detected neither in man nor in rat urine.Because of its particular behaviour toward electrophiles, 5-hydroxy-tienilic acid was found to react with diazomethane with the formation of a complex mixture of methylated products. This made difficult its measurement by a previously described GLC technique, after acidic extraction and methylation by diazomethane. A new very simple assay using HPLC and direct injection of urine is described in this paper. This assay led to a very precise and reproductible determination of tienilic acid and its hydroxylated metabolite in urine.Up to 50% of tienilic acid is excreted in man or rat urine as 5-hydroxy-tienilic acid whereas this metabolite does not appear in dog urine. These data describe the first example of metabolic hydroxylation of the thiophene ring.     

Pharmacokinetics of iododoxorubicin in the rat, dog, and monkey.

The pharmacokinetics of iododoxorubicin (I-DOX) have been studied after single dose administration in the rat (iv and po), dog (iv and po), and monkey (iv). Plasma levels and amounts in urine were monitored by HPLC for both I-DOX and its biologically active metabolite, iododoxorubicinol (I-DOXOL). Plasma levels of I-DOX after iv administration could be described by a three-exponential curve with extremely fast initial phase. Terminal elimination half-lives of I-DOX were similar, 6-7 hr, in all three species. Body weight-normalized clearance (CL) and distribution volumes (Vd) of I-DOX were lower in the dog, but were similar in rat and monkey. The pharmacokinetic parameters also implied metabolic differences between species. Mean I-DOXOL/I-DOX AUC ratios were 0.02, 0.47, and 0.58, respectively, in rat, dog, and monkey, values considerably lower than reported in human studies. I-DOXOL remained slightly longer in the body than I-DOX, as seen both from terminal half-lives (9-11 hr) and mean residence times. In all species, renal excretion was virtually negligible: the amount of I-DOX + I-DOXOL in urine was less than 2% of dose. Mean bioavailabilities of I-DOX were 0.23 and 0.46 in rat and dog, respectively, and, in the latter, about half of I-DOXOL formation occurred during or before the first pass.     

Metabolism of the calcium antagonist gallopamil in man

The metabolism of gallopamil (5-[(3,4-dimethoxyphenyl)methylamino]-2-(3,4,5-trimethoxyphenyl) -2- isopropylvaleronitrile hydrochloride, Procorum, G) was studied after single administration (2 mg i.v., 50 mg p.o.) of unlabelled and labelled G (14G, 2H). TLC, HPLC, GLC, MS and RIA were used for assessment of G and its metabolites in plasma, urine and faeces. G clearance is almost completely metabolic, with only minimal excretion of unchanged drug. Metabolites represent most of the plasma radioactivity after p.o. administration. They are formed by N-dealkylation and O-demethylation with subsequent N-formylation, or glucuronidation, respectively. Compound A, derived by loss of the 3,4-dimethoxyphenethyl moiety of G is the main metabolite in plasma and urine (about 20% of the dose). This metabolite is accompanied by its N-formyl derivative (C), by the N-demethylated compound (H) and the acid (F), formed by oxidative deamination of A. Only 3 unconjugated monphenoles from several O-demthylated products showed distinct plasma levels which were nevertheless lower than metabolite A. These metabolites had no relevance to the pharmacodynamic action. Conjugated monophenolic and diphenolic products represented the major part in plasma and were excreted predominantly via the bile: they represented almost the whole faecal metabolite fraction. Less than 1% of the dose was recovered unchanged in the urine. About 50% of the dose is excreted by urine and 40% by faeces.     

Metabolism and disposition of p-chloroaniline in rat, mouse, and monkey.

The metabolism and disposition of [14C]p-chloroaniline was studied in the male Fisher 344 rat, female C3H mouse, and male rhesus monkey. Greater than 90% of the radiocarbon is eliminated through the urine in all species. A major route of metabolism is orthohydroxylation, whereby 2-amino-5-chlorophenyl sulfate is the major excretion product in all species. Excretion of p-chloro-oxanilic acid and p-chloroglycolanilide, oxidation products of p-chloroacetanilide, is significant in the rat. The appearance of p-chloroacetanilide along with p-chloroaniline in plasma after an oral dose of [14C]p-chloroaniline also was studied in rhesus monkey. In addition to p-chloroacetanilide, 2-amino-5-chlorophenyl sulfate is found to be a major circulating metabolite.     

Biotransformation of nimodipine in rat, dog, and monkey

14C-labelled (+/-) 3-isopropyl5-(2-methoxyethyl)1,4-dihydro-2,6-dimethyl-4- (3-nitrophenyl)-pyridine-3,5-dicarboxylate (nimodipine, Bay e 9736, Nimotop; CAS 66085-59-4) was administered orally to rat, dog, and monkey (each 5, 10, or 20 mg/kg) and intraduodenally to rat (5 mg/kg). Urine was collected over a period of 24 h (bile 6 h). Dog bile was obtained from the gall bladder 4 h after oral dosing. Rat plasma was taken 1 h p. appl. of the unlabelled compound and additionally at different times following administration of [14C]nimodipine. The metabolite profiles in the excreta were established by TLC (radioscan/autoradiography). The unchanged drug was neither detectable in urine nor in bile, but was present in rat plasma. Nimodipine was extensively metabolized. 18 metabolites were isolated by LC, HPLC, and preparative TLC and identified by comparison with the reference substances using two-dimensional TLC, HPLC, GC/radio-GC, 1H-NMR-spectroscopy, MS, and GC/MS. About 75% of the renally excreted biotransformation products, more than 50% of the metabolites present in the bile (rat, dog) and approx. 80% of the plasma metabolites (rat only) have been identified. The large number of metabolites was produced by some common biotransformation reactions: dehydrogenation of the 1,4-dihydropyridine system, oxidative ester cleavage, oxidative O-demethylation and subsequent oxidation of the resulting primary alcohol to the carboxylic acid, hydroxylation of the methyl groups at 2- or 6-position, hydroxylation of one methyl group of the isopropyl ester moiety, reduction of the aromatic nitro group, and glucuronidation as phase II-reaction.     

Identification of ibopamine metabolites in rat and dog urine

Metabolism of ibopamine (N-methyldopamine-O,O'-diisobutyryl ester) was studied in rats and dogs. The compound was well absorbed in both species when given orally. Most of the administered radiolabel (74-94%) was excreted within 24 hr in urine of both species. The major metabolite in rat urine was 4-glucuronylepinine (63% of the total administered dose). Minor metabolites identified were 4-O-glucuronyl-3-O-methylepinine, 3,4-dihydroxyphenylacetic acid (DOPAC), DOPAC-glucuronide, homovanillic acid (HVA), and HVA-glucuronide. Free epinine and epinine sulfate were detected in the range of less than 1% of the total administered dose. Metabolite patterns in dog urine were different from those of rat urine. The major metabolite was epinine-3-O-sulfate (62% of the total administered dose). Minor metabolites identified in dog urine were DOPAC-sulfate, HVA-sulfate, and free HVA. Free epinine was detected but in the range of less than 1% of the total administered dose. These results showed that ibopamine underwent extensive hydrolysis in vivo to epinine, which was subsequently conjugated and excreted as major metabolites in urine. In addition, side chain degradation of epinine led to minor metabolites, which were excreted in urine as free and conjugated forms. The route of conjugation of ibopamine metabolites is species dependent.     

Glucoside formation as a novel metabolic pathway of pantothenic acid in the dog

Metabolism of pantothenic acid (PaA) in beagle dogs was investigated. The dogs excreted 12.3% of the dose in the urine within 24 hr after a single oral administration of [3H]PaA (3 mg/kg). High performance liquid chromatographic analysis of the urine showed the presence of unchanged vitamin and a major metabolite, which accounted for 60.2 and 39.8% of the urinary radioactivity respectively. Although the metabolite was hydrolyzed by treatment with beta-glucuronidase or acid phosphatase, it was found that this hydrolysis resulted from the actions of beta-glucosidase contained as a contaminant in these enzyme preparations. beta-Glucosidase completely hydrolyzed the metabolite to generate PaA and glucose. The metabolite was isolated and subjected to GC/MS and NMR analyses. It was identical to synthetic PaA beta-glucoside, 4'-O-(beta-D-glucopyranosyl)-D-pantothenic acid. It was shown by the use of dog liver microsomes that PaA underwent beta-glucosidation in the presence of uridine diphosphate glucose (UDPG). It is proposed that beta-glucosidation by UDP-glucosyltransferase is a novel metabolic pathway of PaA in the dog.