Non-ionic diffusion and the excretion of weak acids and bases

Milne, M. D.; Scribner, Belding H.; Crawford, M. A.

doi:10.1016/0002-9343(58)90376-0

Cited by 362 publications

(103 citation statements)

References 83 publications

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“…Indeed, urinary pH was found to affect the renal excretion of methadone (clearance) but also its volume of distribution [43]. Urinary pH modulates renal excretion of a number of drugs by the mechanism of nonionic diffusion as described by Milne et al [45]. The absorption and excretion of THC should also be affected by the pH of saliva and urine, which could explain the observed variability.…”

Section: Discussionmentioning

confidence: 95%

Comparison of Cannabinoid Concentrations in Plasma, Oral Fluid and Urine in Occasional Cannabis Smokers After Smoking Cannabis Cigarette

et al. 2016

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-Purpose. A randomized cross-over, double blind placebo controlled study of smoked cannabis was carried out on occasional cannabis smokers. The objective of this research was to describe the pharmacokinetic parameters of THC and its metabolites in plasma, oral fluid and urine, from samples obtained simultaneously to provide estimations of THC and metabolites concentrations after smoking a cannabis cigarette. Methods. Blood, oral fluid and urine samples were collected until up to 72 h after smoking the cannabis cigarette (4% of delta-9-tetrathydrocannabinol (THC)). THC, 11-OH-THC and THC-COOH were analyzed by gas-chromatography-mass spectrometry. Pharmacokinetic parameters were estimated from these data. Results. Eighteen male healthy adults participated in the study. In total, 560 plasma, 288 oral fluid and 448 urine samples were quantified for cannabinoids. Plasma, oral fluid and urine pharmacokinetic parameters were calculated. A wide range of median THC Cmax (1.6-160.0 µg/L and 55.4-123120.0 µg/L in plasma and oral fluid, respectively), 11-OH-THC Cmax (0-11.1 µg/L in plasma) and THC-COOH Cmax (1.0-56.3 µg/L in plasma) was observed. When expressed as a percentage of the total available THC dose, and corrected for molar equivalents, mean percentage of total THC dose excreted was 1.9 +/-2.5 % with range of 0.2-7.5%. This high inter-individual variability was also observed on other calculated pharmacokinetic parameters. Conclusion. Prediction of plasma THC concentration from THC oral fluid concentration or from THC-COOH urinary concentrations is not feasible due to the large variations observed. The results from this study support the assumption that a positive oral fluid THC result or a positive urine fluid result are indicative of a recent cannabis exposure.

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Section: Discussionmentioning

confidence: 95%

Comparison of Cannabinoid Concentrations in Plasma, Oral Fluid and Urine in Occasional Cannabis Smokers After Smoking Cannabis Cigarette

et al. 2016

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“…These lesions are considered to be related to the cytotoxic effects developing due to chemical irritation of the cells by ammonium ions or free ammonia which passes across the cell membranes (Milne et al 1958;Warren 1962). The pathological changes in the organs might also be related to tissue ischaemia and hypoxia occurring due to generalised venous congestion and marked increase in central venous pressure associated with failing cardiovascular and respiratory functions.…”

Section: Resultsmentioning

confidence: 99%

Studies of Clinico-biochemical and Pathological Changes in the Urea-Induced Acute Rumen Alkalosis in Buffalo Calves

Randhawa¹,

Dhaliwal²,

Gupta³

et al. 1989

Acta Vet. Brno

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Randhawa S. S., P. S. Dhaliwal, P. P. Gupta, A. K. Ahuja, S. S. R a th 0 r : Studies on Clinico-biochemical and Pathological Changes in the Urea-Induced Acute Rumen Alkalosis in Buffalo Calves. Acta vet. Brno, 58, 1989: 225-243. Peracute rumen alkalosis was induced by intraruminal administration of urea @ 1.25 g/kg. b. wt. as a single dose in six healthy male Murrah buffalo calves of about 1 -2 years age. Peracute ammonia toxicity resulted in profuse salivation, ruminal stress, incoordination, recumbency followed by clonic convulsions, frequency of which increased with the progression of the condition, dyspnea, hyperpnea, tachycardia, opisthotonus, pupillary dilatation followed by death of the animals between 60-150 mts. It was observed that a linear relationship exists between death time and body weight of the calf with the same dose rate. Electrocardiographic studies revealed ventricular fibrillation with superimposition of P wave over T wave. The cardiac potentials gave rise to random osci11ations. Studies on liver function tests revealed that ammonia toxicity markedly affects the functional status of the liver as indicated by increase in serum enzymatic activities of arginase, glutamic oxalotransaminase, glutamic pyruvic transaminase, lactate dehydrogenase and glutamate dehydrogenase with increase in the half life of B.S.P. excretion rate which was subsequently confirmed by histopathological observations. Histopathological changes in the digestive system revealed exfoliation of the epithelial lining of the mucous membrane of the rumen, lymphocytic abomasitis, and necrotic enteritis. Other significant histopathological alterations were follicular cholecystitis, meningo-encephalitis, lymphocytic nephritis and cystitis, and alveolar emphysema. Intoxication, ECG, rumen liquor, blood, urineSudden changes in the dietary constituents with consumption of excess amounts of protein-rich concentrates and/or non-protein nitrogenous compounds has resulted in frequent occurrence of rumen alkalosis in ruminants. The disease is characterised by excessive production of ammonia in the rumen which may produce gastrointestinal, hepatic, renal, circulatory and nervous disturbances (Chalupa 1968; Parkins et aI.

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“…Milne, Scribner and Crawford (22) (23). Organic acid excretion would thus become a function of pH in the tubule cells rather than of urinary pH or general changes in acid-base balance of the body.…”

Section: Discussionmentioning

confidence: 99%

THE EXCRETION OF l-MALIC ACID IN RELATION TO THE TRICARBOXYLIC ACID CYCLE IN THE KIDNEY*

Vishwakarma¹,

Lotspeich²

1959

J. Clin. Invest.

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Non-ionic diffusion and the excretion of weak acids and bases

Cited by 362 publications

References 83 publications

Comparison of Cannabinoid Concentrations in Plasma, Oral Fluid and Urine in Occasional Cannabis Smokers After Smoking Cannabis Cigarette

Comparison of Cannabinoid Concentrations in Plasma, Oral Fluid and Urine in Occasional Cannabis Smokers After Smoking Cannabis Cigarette

Studies of Clinico-biochemical and Pathological Changes in the Urea-Induced Acute Rumen Alkalosis in Buffalo Calves

THE EXCRETION OF l-MALIC ACID IN RELATION TO THE TRICARBOXYLIC ACID CYCLE IN THE KIDNEY*

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