Observation of dipole-dipole interaction in a degenerate quantum gas.

We have investigated the expansion of a Bose-Einstein condensate of strongly magnetic chromium atoms. The long-range and anisotropic magnetic dipole-dipole interaction leads to an anisotropic deformation of the expanding chromium condensate which depends on the orientation of the atomic dipole moments. Our measurements are consistent with the theory of dipolar quantum gases and show that a chromium condensate is an excellent model system to study dipolar interactions in such gases.

Observation of Feshbach resonances in an ultracold gas of 52Cr.

We have observed Feshbach resonances in collisions between ultracold 52Cr atoms. This is the first observation of collisional Feshbach resonances in an atomic species with more than one valence electron. The zero nuclear spin of 52Cr and thus the absence of a Fermi-contact interaction leads to regularly spaced resonance sequences. By comparing resonance positions with multichannel scattering calculations we determine the s-wave scattering length of the lowest (2S+1)Sigma(+)(g) potentials to be 112(14) a(0), 58(6) a(0), and -7(20) a(0) for S=6, 4, and 2, respectively, where a(0)=0.0529 nm.

Disposition and cardioselectivity of MDL 74,405, a vitamin E-like free radical scavenger, in rats and dogs after intravenous infusion.

The disposition kinetics of MDL 74,405, a potent free radical scavenger for cardiac reperfusion and a vitamin E analog, was investigated in rats (1.2, 6.0, and 12 mg/kg) and dogs (1 and 10 mg/kg) after an intravenous infusion. Because the heart is the target site of drug action, a tissue distribution study was also conducted in rats (1.2 mg/kg) to explore the affinity of the drug to rat heart. In both animal species, plasma drug concentrations declined rapidly in the early distribution phase and exhibited a multiexponential pattern of elimination. Of the total excretion (95-96% of the dose) in 120 hr in rats, 45-51% was excreted in urine and 45-50% in feces. Of the total excretion (86-89% of the dose) in 120 hr in dogs, 41-43% of the dose was excreted in urine and 41-43% in feces. The dose was excreted mainly unchanged (62-78% in rat and 80-86% of the dose in dog urine) with several potential minor metabolites, indicating that renal and biliary excretions are the two major, equally important, routes of drug elimination in both species. Rats cleared the drug from the body markedly faster than dogs: the mean residence time in rats. (1.9-3.2 hr) was 15-20 times shorter, the terminal elimination half-life in rats (3.6-7.0 hr) was 10 times shorter; and the total clearance in rats (148-216 ml/min/kg) was 6-9 times greater. The steady-state volume of distribution was very large for both species. (19-37 liters/kg for rats and 59-64 liters/kg for dogs), which is consistent with the extensive tissue uptake of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Disposition of a new diacid angiotensin-converting enzyme inhibitor after intravenous administration of drug or prodrug to monkeys and dogs.

The disposition of [4S-[4 alpha,7 alpha,(R*),12b beta]]-7- [S-(1-carboxy-3-phenylpropyl)amino]-1,2,3,4,6,7,8,12b-octahydro-6- oxo- pyrido[2,1-a][2]benzazepine-4-carboxylic acid (MDL 27,088), a new a new angiotensin-covering enzyme inhibitor, was studied in cynomolgus monkeys and beagle dogs given intravenous (iv) doses of MDL 27,088 or its prodrug, MDL 27,210. Although in both species iv-administered MDL 27,210 was extensively (> 99.9%) metabolized and excreted in the urine and feces as MDL 27,088, the disposition of MDL 27,088 appeared to be significantly influenced by its mode of administration. For example, the mean terminal half-life of MDL 27,088 in plasma was longer when MDL 27,088 was given as its prodrug (3.65 and 2.23 h in monkeys and dogs, respectively) than when it was administered directly (0.84 and 1.05 h in monkeys and dogs, respectively). The renal excretion of MDL 27,088 also increased (from 33 to 73% of the dose in monkeys and from 9 to 17% of the dose in dogs) when MDL 27,088 was administered directly versus when it was given as its prodrug. These and other results of this study suggest that the disposition of MDL 27,088 can be significantly altered by iv administration of its prodrug form. Such changes in disposition also suggest that iv administration of prodrug may influence the pharmacological activity of MDL 27,088.

Disposition and metabolism of the angiotensin-converting enzyme inhibitor [4S-[4 alpha, 7 alpha, (R*), 12b beta]]-7-[S-(1-ethoxycarbonyl-3- phenylpropyl)amino]-1,2,3,4,6,7,8,12b-octahydro-6-oxo- pyrido[2,1-a][2]benzazepine-4-carboxylic acid in monkeys and dogs.

[4S-[4 alpha, 7 alpha, (R*),12b beta]]-7-[S- (1-ethoxycarbonyl-3-phenylpropyl)amino]-1,2,3,4,6,7,8, 12b-octahydro-6-oxo-pyrido[2,1-a][2]benzazepine-4-carboxylic acid (MDL 27,210) is the ethyl ester prodrug of a potent angiotensin-converting enzyme inhibitor, MDL 27,088. After a single dose of [14C]MDL 27,210 (3 mg/kg iv), MDL 27,210 was rapidly eliminated from the plasma of monkeys and dogs with a terminal half-life of approximately 0.3 hr. The steady-state volume of distribution was 0.15 liter/kg in dogs and 0.28 liter/kg in monkeys. Monkeys excreted 52% of the 14C dose in the feces and 41% in the urine; dogs excreted 80% of the 14C dose in the feces and 14% in the urine. The presence of a large fraction of the 14C dose in the feces of both species following iv administration suggests that significant biliary excretion occurred. MDL 27,210 administered iv to monkeys and dogs was rapidly and extensively (greater than 99.9%) metabolized, primarily to its diacid metabolite, MDL 27,088. The half-life of MDL 27,088 was 2.2 hr in dogs and 3.6 hr in monkeys.