The pharmacokinetics of the weakly protein-bound anionic compound diatrizoate in serum and synovial fluid of the horse.

PURPOSE: To establish a pharmacokinetic model for the model drug, sodium diatrizoate (DTZ), allowing joint disappearance kinetics to be estimated from serum appearance kinetics following intra-articular administration, and to calculate the relative joint exposure after intravenous and intra-articular DTZ administration (F(iv/IA)). METHODS: Each of five horses received an aqueous solution of 3.9 mg/kg sodium diatrizoate both intravenously and intra-articularly separated by a one-week wash out period. Serum and synovial samples were collected over 7 h and analyzed for content of model compound using inductively coupled plasma mass spectrometry. RESULTS: Differential equations were used for describing the transport of DTZ between the joint and the central compartment. The three-compartment lag-time model obtained demonstrates that the rate of drug appearance in the systemic circulation equals the rate of disappearance from the joint compartment. Following intravenous and intra-articular administration, an average F(iv/IA) of 0.04% (n = 4) was calculated based on the synovial fluid profiles of DTZ. CONCLUSIONS: This study implies that aspects of the intra-articular fate of DTZ can be obtained from serum data in case synovial fluid samplings are limited, for various possible reasons. The low F(iv/IA) may stimulate future research in the field of intra-articular administration of anti-osteoarthritic drugs.

[Absorption of L-lysine diatrizoate from the gastrointestinal tract: the influence of surgery, inflammation and neoplasia]. / Resorption von L-Lysin-Diatrizoat aus dem Gastrointestinaltrakt unter dem Einfluss von Operation, Entzündung und Neoplasie.

PURPOSE: To ascertain whether the absorption of L-lysine diatrizoate, a sodium-free salt of the contrast-giving diatrizoic acid, from the gastrointestinal tract is increased by surgery, inflammation or neoplasia. MATERIAL AND METHODS: Using contrast medium containing L-lysine diatrizoate for intestinal opacification, this prospective study compared 32 radiographic examinations of the upper gastrointestinal tract with 52 radiographic examination of the lower gastrointestinal tract. In blood samples taken from the patients immediately after the radiographic examinations, the concentration of diatrizoic acid was determined by high pressure liquid chromatography. The results were correlated with sex, age, surgical history and any evidence of inflammatory or neoplastic diseases. RESULTS: The serum diatrizoic acid concentration in patients after oral administration was 3.62 (95% CI, 2.86 - 10.17) microg/ml. The titer was lower in patients who had undergone abdominal surgery than in patients without surgery. Serum diatrizoic acid concentration in patients after rectal administration was 0.30 (95% CI, 0.13 - 0.60) microg/ml. The titer was significantly higher (p < 0.05) in patients suffering from inflammatory conditions or neoplasms than in the other patients. CONCLUSION: The L-lysine salt of diatrizoic acid is absorbed in larger amounts from the upper than from the lower gastrointestinal tract. Absorption is not increased after abdominal surgery. However, inflammatory conditions and neoplasms of the large bowel increase the uptake of contrast medium from the intestine.

Bolus dynamics: theoretical and experimental aspects.

This paper analyses the arterial enhancement produced by short intravenous boluses of iodinated contrast medium, with particular attention to the differences between various types of contrast media. A theoretical discussion is presented, followed by a small experimental study. The characteristics of the arterial time-attenuation curve are a function of the rate of contrast medium transit to the extracellular fluid (ECF), osmolality driven transit of water from the ECF into the plasma, direct effects on the heart and pulmonary circulation, the distribution of transit times in the cardiopulmonary circulation and recirculation. Theory predicts that while differences in peak arterial attenuation/peak height (PH) will be small, alterations in the areas under the time-attenuation curve (AUC) will reflect early-phase rate constants in the absence of major inotropic effects. The AUC should be higher for non-ionic than ionic media reflecting these lower rate constants. An experimental study on three healthy dogs confirmed these theoretical observations, with a slightly higher PH (6.5% higher) using a non-ionic medium but a substantially higher AUC (22% higher). (Differences significant at the 5% level, two-tailed paired t-test.) Our theoretical predictions and experimental findings suggest non-ionic media produce superior vascular enhancement, particularly shortly after injection. Possible clinical implications, particularly in dynamic enhanced computed tomography, are discussed.

Comparison of measurement of glomerular filtration rate by single sample, plasma disappearance slope/intercept and other methods.

Various in vitro methods employing radioactive indicators have been presented for the determination of glomerular filtration rate (GFR) including slope/intercept (S/I) and single sample (SS) methods. The S/I technique utilizes the analysis of the slope of a certain segment of the plasma disappearance curve of a suitable radioactive indicator and its intercept on the y axis. The SS method is based on the theoretical volumes of distribution derived from a single plasma concentration at some specific time after intravenous injection of the indicator. Using GFRs estimated from the compartmental analysis of the entire plasma disappearance curve as a reference standard, we have compared the errors of GFR estimation calculated from 12 S/I methods, 3 SS methods and 2 techniques in which original formulae were derived. The errors of the SS method of Tauxe et al. gave the lowest standard error of estimate (Sy X x) of all the methods. The S/I methods gave lowest errors when sampling times were taken between 60 min and 240 min. Almost all the errors observed here were significantly less than those observed using scintillation camera techniques. The SS method seems to be the method of choice for estimation of GFR by single injection techniques. The use of the scintillation camera in conjunction with the SS technique would provide a useful right to left ratio so that individual kidney GFR could be calculated.

[Determination of the binding of 3,5-bis(acetamido)-2,4,6-triiodobenzoic acid and some of its salts to human serum albumin using the ultrafiltration flat chamber method]. / Bestimmung der Bindung von 3,5-Bis-(acetamido)-2,4,6-trijodbenzoesäure sowie einigen ihrer Salze an Humanserumalbumin mit Hilfe der Ultrafiltrationsflachkammer-Methode.

Using the ultrafiltration flat chamber method the binding of N-methylglucamine, meglumine amido trizoate, lysine amido trizoate, diatrizoic acid and L-lysine to human serum albumin (HSA) was investigated. It was demonstrated that the affinity to HSA decreases in the above mentioned order. Binding was characterised by determination of K1 (total binding constant), k+ (apparent binding constant), n (number of binding sites per molecule of albumin) and delta F degrees (free reaction energy).

Analysis of iosulamide in plasma and urine: application to intravenous pharmacokinetics in rhesus monkey.

A sensitive, specific, high-performance liquid-chromatographic method for the determination of iosulamide in plasma and urine is described. The method was used to determine pharmacokinetic parameters of iosulamide after intravenous administration to rhesus monkeys. The mean (+/- SE) distribution and disposition half-lives were 0.19 (+/- 0.03) and 1.5 (+/- 0.3) hr, respectively. The mean (+/- SE) model-dependent and model-independent volumes of distribution at steady state were 0.41 +/- (0.078) and 0.49 (+/- 0.039) liters/kg, respectively. Total urinary excretion of iosulamide represented a mean (+/- SE) of 12.5 (+/- 0.6)% of the administered dose and was virtually complete in 3 hr. The results of the pharmacokinetic study indicate that iosulamide is rapidly cleared from the body and that renal clearance is a minor route of elimination from the body.

The distribution of 125I-metrizamide and 125I-diatrizoate between blood, brain and cerebrospinal fluid in the rabbit.

The entry of 125I-metrizamide and of 125I-diatrizoate from blood into brain has been studied in rabbits. The blood-brain barrier is very tight to both molecules, all cerebral regions having spaces between 0.5 and 2% after maintenance of constant blood levels for 4 h. In extraneural tissues both compounds appear to distribute in extracellular fluid except for accumulation of metrizamide by the liver and perhaps the small intestine. Profiles of radioactivity through cerebral gray matter have been obtained following ventriculocisternal perfusion of artificial cerebrospinal fluid containing 125I-metrizamide. The nature of these profiles and their behavior with time suggest that metrizamide passes through gray matter by simple diffusion, that it is largely distributed in the extracellular fluid and that bake movement across the blood-brain barrier is small.