The effect of physical conditioning on antipyrine clearance

Clinical Pharmacology and Therapeutics, 1984

Physical fitness, as expressed by maximal oxygen uptake (1.702max), was measured in 14 subjects before and during physical education consisting of 4 to 8 hr of daily physical training. Mean pulse rate during training was 115 bpm. After 3 mo of physical training, f/02 max increased a mean 6% (range 5% to +23%). Corresponding mean increases in hepatic drug metabolism, as expressed by the metabolism of the model drugs antipyrine and aminopyrine, were 12% (range 12% to +59%) and 13% (range 21% to +47%). Changes in the two groups were still present 6 mo after physical education. There was only a moderately close but nonetheless significant correlation (r = 0.7) between the extent of change inf702max and the corresponding relative change in antipyrine metabolism during the 3-mo period of this investigation. The correlation between oxygen uptake and aminopyrine metabolism (r = 0.6) was slightly less and was not significant. Improved physical fitness associated with enhanced drug metabolism may lead to changes in drug efficacy and drug toxicity that may be clinically important in the case of drugs with low therapeutic indices.

European journal of applied physiology, 2000

Drug metabolizing capacity is generally reduced in the elderly, and physical exercise has been reported to increase drug oxidative metabolism. The purpose of this investigation was to study the effects of engagement in a program of regular physical exercise on the clearance and metabolite excretion of antipyrine, a marker of oxidative metabolism, in elderly subjects. The saliva clearance of antipyrine and the production clearances of antipyrine metabolites were studied in 37 elderly women (mean age 66 years). Subjects attended 60-min sessions three times a week for 12 weeks. Each session consisted of both aerobic (training of cardiorespiratory capacity) and nonaerobic (training of muscular strength/endurance and flexibility/coordination) exercises performed at 50–75% of maximum oxygen uptake. Antipyrine was administered orally and pharmacokinetic parameters were obtained from saliva and urine samples. After 3 months of participation in the exercise program, salivary antipyrine clearance was significantly increased by 17% mean (SEM) 0.42 (0.02) vs 0.36 (0.02) ml/min/kg; P < 0.05) and the half-life of antipyrine was significantly reduced by 18% (17.9 (1.1) vs 22.3 (1.3) h; P < 0.05). No significant change with exercise was observed in the renal clearance of antipyrine or in the norantipyrine formation clearance, but significant increases were found for hydroxymethylantipyrine [42 (5) vs 32 (4) μl/kg/min; P < 0.05; +31%] and 4-hydroxyantipyrine [243 (18) vs 194 (17) μl/kg/min; P < 0.05; +25%] formation clearances. These findings indicate that regular exercise leads to increased disposition of antipyrine in the elderly and that the main metabolic pathways of the compound are changed differentially.

2000

According to the limited information available, exercise has no substantial effect on the absorption of orally given drugs. However, it appears to enhance absorption from intramuscular, subcutaneous, transdermal and inhalation sites. The effects of exercise on drug distribution are complex. Exercise increases muscular blood flow resulting, for example, in the increased binding of digoxin in working skeletal muscle. On the other hand, exercise may sequester some drugs such as propranolol in muscle and reduce the availability of the drug for elimination. In addition, exercise decreases the clearance of highly extracted drugs and increases their plasma concentration. It may also increase the clearance of drugs by increasing biliary excretion. Since exercise reduces renal blood flow, the plasma concentrations of those drugs which are primarily eliminated by the kidneys may increase. In conclusion, if maintaining the plasma concentration of a drug at a certain level is important, consideration should be given to alternative drugs if the patient is on intermittent or irregular exercise.

British Journal of Clinical Pharmacology, 2001

Aims Pseudoephedrine (PSE) is a readily available over-the-counter nasal decongestant which is structurally similar to amphetamine and is included on the International Olympic Committee's list of banned substances. However to date, little research has supported its putative ergogenic effect. This study investigated whether a 180 mg dose of PSE ingested 45 min prior to exercise enhanced short-term maximal exercise performance and/or altered related physiological variables. Methods A randomised, double-blind, crossover study in 22 healthy male athletes. Results Maximum torque (mean t s.d., n=22) produced in an isometric knee extension exercise was 321.1t62.0 Nm (PSE) and 295.7t72.4 Nm (placebo), and peak power obtained on the`all-out' 30 s cycle test was 1262.5t48.5 W (PSE) and 1228.4t47.1 W (placebo) (P<0.01, P<0.03, respectively). Subjects were estimated to be producing 96.9t2.4% of their maximal possible isometric leg extension force after PSE ingestion, but only 95.3t2.4% when PSE was not ingested. Bench press tasks and total work during the cycle test were not affected by the ingestion of PSE. Lung function was altered following ingestion of PSE (P<0.05) with FEV 1 and FVC signi®cantly increased (P<0.02, P<0.01, respectively) although the FEV 1 /FVC ratio was not altered. Heart rate was signi®cantly elevated by the ingestion of PSE immediately following the 30 s cycle sprint (P<0.01) however, lactate concentration was not altered by the ingestion of PSE. Conclusions The administration of a 180 mg dose of PSE increased maximum torque, produced in an isometric knee extension and produced an improvement in peak power during maximal cycle performance, as well as improving lung function.

Purpose: This study examined the influence of preexercise food intake on plasma pseudoephedrine (PSE) concentrations and subsequent high-intensity exercise. In addition, urinary PSE concentrations were measured under the same conditions and compared with the present threshold of the World Anti-Doping Agency (WADA). Methods: Ten highly trained male cyclists and triathletes (age = 30.6 T 6.6 yr, body mass [BM] = 72.9 T 5.1 kg, and V O 2max = 64.8 T 4.5 mLIkg j1 Imin j1 ; mean T SD) undertook four cycling time trials (TT), each requiring the completion of a set amount of work (7 kJIkg j1 BM) in the shortest possible time. Participants were randomized into a fed or nonfed condition and orally ingested 2.8 mgIkg j1 BM of PSE or a placebo (PLA) 90 min before exercise; in the fed trials, they consumed a meal providing 1.5 gIkg j1 BM of CHO. Venous blood was sampled at 30, 50, and 70 min and pre-warm-up and postexercise for the analysis of plasma PSE and catecholamine concentrations, and urine was also collected for the analysis of PSE concentration. Results: Independent of the preexercise meal, 2.8 mgIkg j1 BM of PSE did not significantly improve cycling TT performance. The fed trials resulted in lower plasma PSE concentrations at all time points compared with the nonfed trials. Both plasma epinephrine and blood lactate concentrations were higher in the PSE compared with the PLA trials, and preexercise and postexercise urinary PSE concentrations were significantly higher than the threshold (150 KgImL j1) used by WADA to determine illicit PSE use. Conclusion: Irrespective of the preexercise meal, cycling TT performance of approximately 30 min was not improved after PSE supplementation. Furthermore, 2.8 mgIkg j1 BM of PSE taken 90 min before exercise, with or without food, resulted in urinary PSE concentrations exceeding the present WADA threshold.

Acta Physiologica Scandinavica, 1993

The effect of intermittent high-intensity training on the activity of enzymes involved in purine metabolism and on the concentration of plasma purines following acute shortterm intense exercise was investigated. Eleven subjects performed sprint training three times per week for 6 weeks. Muscle biopsies for determination of enzyme activities were obtained prior to and 24 h after the training period. After training, the activity of adenosine 5'-phosphate (AMP) deaminase was lower (P < 0.001) whereas the activities of hypoxanthine phosphoribosyl transferase (HPRT) and phosphofructokinase were significantly higher compared with pre-training levels. The higher activity of HPRT with training suggests an improved potential for rephosphorylation of intracellular hypoxanthine to inosine monophosphate (IMP) in the trained muscle. Before and after the training period the subjects performed four independent 2-min tests at intensities from a mean of 106 to 135 % of Vozma,. Venous blood was drawn prior to and after each test. The accumulation of plasma hypoxanthine following the four tests was lower following training compared with prior to training (P < 0.05). The accumulation of uric acid was significantly lower (46% of pre-training value) after the test performed at 135% of VoZmax (P < 0.05). Based on the observed alterations in muscle enzyme activities and plasma purine accumulation, it is suggested that high intensity intermittent training leads to a lower release of purines from muscle to plasma following intense exercise and, thus, a reduced loss of muscle nucleotides.

The main objective of the five-thousand-meter race in the present study is improving and developing the time taken by the runner. Beta-Alanine is highly important in reducing lactic acid during training and control muscle fatigue. Data showed that the legalized training program improves the physical and physiological abilities and the numerical achievement of 5000 meters running in accordance with the speed strategy and physiological indicators. This affects developing values of respiratory circulatory system's indicator and aerobics and nonaerobic training that improve respiratory system responses' variables by 7.49%; including maximum absolute and relative oxygen consumption. The current study also showed that no moral differences with the statistical references in liver enzymes (SGPT-SGOT-GGT) wither before or after the stress of the experimental group that received Beta-Alanine, which confirms the viability of liver enzymes. The study concluded that taking Beta-Alanine associated with the training program of the 5000 meter runners resulted in improving the physiological indicators (lactic acid and maximum oxygen consumption).

International Journal of Sport Nutrition & Exercise Metabolism, 2010

The aim of the current study was to investigate the effect of 180 mg of pseudoephedrine (PSE) on cycling time-trial (TT) performance. Six well-trained male cyclists and triathletes (age 33 ± 2 yr, mass 81 ± 8 kg, height 182.0 ± 6.7 cm, VO 2max 56.8 ± 6.8 ml • kg-1 • min-1 ; M ± SD) underwent 2 performance trials in which they completed a 25-min variable-intensity (50-90% maximal aerobic power) warm-up, followed by a cycling TT in which they completed a fixed amount of work (7 kJ/kg body mass) in the shortest possible time. Sixty minutes before the start of exercise, they orally ingested 180 mg of PSE or a cornstarch placebo (PLA) in a randomized, crossover, double-blind manner. Venous blood was sampled immediately pre-and postexercise for the analysis of pH plus lactate, glucose, and norepinephrine (NE). PSE improved cycling TT performance by 5.1% (95% CI 0-10%) compared with PLA (28:58.9 ± 4:26.5 and 30:31.7 ± 4:36.7 min, respectively). There was a significant Treatment × Time interaction (p = .04) for NE, with NE increasing during the PSE trial only. Similarly, blood glucose also showed a trend (p = .06) for increased levels postexercise in the PSE trial. The ingestion of 180 mg of PSE 60 min before the onset of high-intensity exercise improved cycling TT performance in well-trained athletes. It is possible that changes in metabolism or an increase in central nervous system stimulation is responsible for the observed ergogenic effect of PSE.

… journal of medicine & science in sports, 1995