Spectrofluorometric Analysis of Cardiotonic Steroids

Wells, David T.; Katzung, Bertram G.; Meyers, Frederick H.

doi:10.1111/j.2042-7158.1961.tb11843.x

Cited by 57 publications

(4 citation statements)

References 7 publications

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“…Although mathematically methods 3 and 4 are equivalent, the values obtained by use of equations 10 and 11 will be different since equation 10 utilizes AUC data while equation 11 utilizes Ae data. Renal clearance of digoxin for each subject after each treatment was estimated as the slope of orthogonal least-squares line (9) when Ae was plotted vs. AUC. Three points were used in each case, corresponding to 0-24, 24-48, and 48-72 hr.…”

Section: Methodsmentioning

confidence: 99%

Comparison of thein vitro andin vivo release of digoxin from four different soft gelatin capsule formulations

Wagner

Stoll

Weidler

et al. 1979

Journal of Pharmacokinetics and Biopharmaceutics

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A blinded, four-treatment crossover study in 16 normal adult male volunteers compared plasma concentrations and urinary excretion of digoxin, measured by radioimmunoassay, after oral administration of soft gelatin capsule formulations of digoxin. Four 0.4-mg formulations with different in vitro "burst times" and dissolution rates were administered, with 2-week intervals between treatments. The two capsules with lowest in vitro burst times (2.9 and 16 min) gave comparable in vivo results. The other two capsules, with in vitro burst times of 62 and 229 min, produced significant delays in digoxin absorption. In vitro-in vivo correlations were obtained by comparing the logarithm of the in vitro burst time with time to peak plasma level and the time to the first measurable plasma level (> or = 0. 05 ng/ml). Also, the mean time to peak plasma level correlated with the logarithm of the time required to release either 50% or 85% of the digoxin in vitro. No significant changes were found in the amount of digoxin absorbed from each capsule as determined by urinary excretion or AUC0-infinity.

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Section: Methodsmentioning

confidence: 99%

Comparison of thein vitro andin vivo release of digoxin from four different soft gelatin capsule formulations

Wagner

Stoll

Weidler

et al. 1979

Journal of Pharmacokinetics and Biopharmaceutics

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“…The mechanism of the Schmidt & Lindenbaum, 1975). The t Correspondence and present address : Medical ~i~i~i~~, Burroughs wellcome c0., 3030 m e capsules were assayed both in bulk and individually using an automated modification of the tluorimetriC method for the determination of digoxin described by Wells, Katzung & Meyers (1961). The t Correspondence and present address : Medical ~i~i~i~~, Burroughs wellcome c0., 3030 m e capsules were assayed both in bulk and individually using an automated modification of the tluorimetriC method for the determination of digoxin described by Wells, Katzung & Meyers (1961).…”

Section: Encapsulation Of a Solution Of Digoxin In Soft Gelatin Is Vamentioning

confidence: 99%

The effects of storage upon in vitro and in vivo characteristics of soft gelatin capsules containing digoxin

Johnson

Mcauley

Smith

et al. 1977

Journal of Pharmacy and Pharmacology

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The effects of both the (+)-and ( -)-enantiomen of VII were reversed by P2S in both tests in the same manner as the effects of any of the ethyl S-alkylmethylphosphonothioates. It is noteworthy that although the (+)-and (-)-isomers of VII inhibit acetylcholinesterase at different rates and substantially faster than the (+)-and (-)-isomers of the S-alkyl methylphosphonothioates (e.g. I( +) and I( -)), the reactivation profiles of all four compounds were indistinguishable.The results of the in vivo experiments showed marked differences from those obtained in vitro. The rank order of the LD50 values did not correspond with the rank order of potency of the compounds in the in vitro tests ( Table 2). Moreover there was sometimes no significant difference between the LD50 values of an enantiomeric pair even though the (-)-isomer was in vitro clearly a more potent anti-acetylcholinesterase than the (+)isomer. In the case of one compound, ethyl S-propyl methylphosphonothioate (I), the (+)-isomer was significantly more toxic than the (-)-isomer in contrast to the results of the in vitro results.In the gastrocnemius muscle, as is shown in Fig. 2, the administration of P2S at a dose of 130pmol kg-l, during poisoning by the (-)-enantiomer of I, reestablished neuromuscular function whereas similar P2S treatment of poisoning by the (+)-enantiomer and the racemate failed to restore neuromuscular function. Compounds I1 and 111 showed similar behaviour. In marked contrast, the effects of both the (+)-and (-)-muscle enantiomers of VII on the gastrocnemius preparation were reversed by administration of p2sThe difference in response to P2S of the (+)-( -)-enantiomen of the ethyl-methylphosphonothioates I, I1 and 111 was consistent with the prelimi observation that rats poisoned by (+)ethyl-smethylphosphonothioate (I+) failed to respond to P2S-atropine treatment. Thus whereas for I(, (Green, Muir & others, 1977) gave a Protection ratio of d 8.5 (protection ratio = LDSO of Sarin in trak e animals/LDSO of Sarin in untreated animals) th protection ratios of I(+) and I(&) were 2.2 and respectively. In marked contrast, but in agreement With the results on the gastrocnemius preparation, p2s, atropine treatment of poisoning by VII( i), VII(+) and VII(-) gave protection ratios Of 24, 70 and 55 respectively. To our knowledge there is no recorded precedent for the difference of the (+)-and (-1-enantiorners of the ethyl-methylphosphonothioates observed in viva. previous comparisons (Fukuto, 1971) of the enanti,,. mers of alkylphosphonothioate anticholinesterases have been concerned mainly with the insecticidal activity and stereoselectivity of cholinesterases from different SO^^^ and so no indications of possible mechanistic in viva differences in animals were obtained. That metabolic activation of the (+)-isomers occurs, is an attractive proposition.

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“…A peroxide-ascorbic acid spectrofluorometric analysis for these cardiotonic steroids is also available (531), as well as an extensive review on the fluorescence reactions of digitalis compounds (165).…”

Section: Aliphatic Compoundsmentioning

confidence: 99%