Amphetamine excretion

Oyler, J.M., Cone, E.J., Joseph, R.E., Moolchan, E.T., and Huestis, M.A., Duration of detectable methamphetamine and amphetamine excretion in urine after controlled oral administration of methamphetamine to humans, Clin. Chem., 48(10), 1703-1714, 2002. 

Oyler JM, Cone EJ, Joseph, Jr RE, Moolchain ET, Huestis MA. Duration of detectable methamplieta-mine and amphetamine excretion in urine after con-... 

Affecting the rate of drug elimination by increasing urinary pH (eg, the excretion of salicylates is increased, whereas excretion of quinidine and amphetamines is decreased)... 

OWENS has prepared antibodies to PCP in goats. When administered to mice the PCP levels in blood rose tenfold as an antibody-bound form that was readily excreted in urine. BROWNE tested the selfadministration by rats of 1,000 compounds related (and not related) to PCP, some of which produced PCP-like effects. One compound that was self-administered prevented the entrance of PCP into brain. BALSTER gave a general review of the effects produced by PCP in laboratory animals and showed that some effects were similar to those produced by amphetamine, some to barbiturates, and some to antipsychotics. This response profile makes PCP a unique drug that stands alone in its complex effects and toxicity. 

The answer is a. (Hardman, pp 16-20.) Sodium bicarbonate is excreted principally in the urine and alkalinizes it. Increasing urinary pH interferes with the passive renal tubular reabsorption of organic acids (such as aspirin and phenobarbital) by increasing the ionic form of the drug in the tubular filtrate. This would increase their excretion. Excretion of organic bases (such as amphetamine, cocaine, phencyclidine, and morphine) would be enhanced by acidifying the urine. 

The consumption indicator is the metabolic byproduct excreted at the highest rate. It may be a metabolite, as it is the case for cocaine (BE) and heroin (MOR), or the drug itself, as it is the case of amphetamine-like compounds. THC, the most psychoactive cannabinoid of the cannabis herb, is highly metabolized before excretion, thus, the consumption indicator selected (THC-COOH) presents an excretion rate of 0.6%. Despite the fact that OH-THC presents a slightly higher excretion rate (2%), this analyte was not selected to back calculate cannabis use due... 

Both acid and alkaline manipulation of urine applies the principle of ion-trapping in the renal tubules. However, acid diuresis is not advocated because of the risk of developing myoglobinuria and acute renal failure. The intent of modifying the urine pH toward an acidic side is to promote the excretion of drugs with an alkaline pKa such as phencyclidine or amphetamine. 

Mecfianism of Action A phenylalkylamine sympathomimetic with activity similar to amphetamines that stimulates the central nervous system (CNS) and elevates blood pressure (BP) most likely mediated via norepinephrine and dopamine metabolism. Causes stimulation of the hypothalamus. Therapeutic Effect Decreases appetite. Pharmacokinetics The pharmacokinetics of phendimetrazine tartrate has not been well established. Metabolized to active metabolite, phendimetrazine. Excreted in urine. Half-life 2-4 hr. 

Pharmacokinetics Rapidly absorbed from the G1 tract. Crosses the blood-brain barrier. Metabolized in the liver to the active metabolites. Primarily excreted in urine. Half-life 17hr (amphetamine), 20 hr (methamphetamine). 

Methylphenidate hydrochloride, a piperidine derivative structurally similar to amphetamine, is a commonly prescribed stimulant for the treatment of ADHD in children age 6 years and older. It is a racemic mixture of d,l methyl a-phenyl-2-piperidineacetate hydrochloride. The drug is available in immediate-release, extended-release, and controlled-release formulations. It is hepatically metabolized to an inactive metabolite and excreted by the kidneys. 

The risk of tachycardia, hypertension, and cardiotoxicity is increased with coadministration of dronabinol (an antiemetic) and dextroamphetamine. In addition, administration of dextroamphetamine with MAOIs may increase the risk of hypertensive crisis. Al-kalinizing agents can speed absorption (e.g., antacids) or delay urinary excretion (e.g., acetazolamide, thiazide diuretics) of dextroamphetamine, thus potentiating its effects. Gastric or urinary acidifying agents (e.g., ascorbic acid, ammonium chloride) can decrease the effects of dextroamphetamine. Propoxyphene overdose can potentiate amphetamine central nervous system stimulation, potentially resulting in fatal convulsions. 

Methamphetamine passes the blood-brain barrier better than amphetamine, and there is evidence that chronic use of methamphetamine can result in permanent damage to dopamine neurons. Both pass the placental barrier, and there is some evidence that abuse by a pregnant woman can result in fetal abnormalities. Methamphetamine is found in breast milk. The half-life of methamphetamine and amphetamine is about 10 to 13 hours. Some methamphetamine is metabolized to amphetamine, and amphetamine-glucuronide can be detected in urine for about two days. About 50% of methamphetamine is excreted unchanged in the urine over two to three days. 

Ammonium chloride increases urinary volume with acidification of urine. The excretion of amphetamine is decreased in relatively alkaline urine and has proved useful in the treatment of amphetamine intoxication. ... 

Methylphenidate is chemically and pharmacologically similar to amphetamine. Both act by releasing norepinephrine and dopamine in brain. Both produce increased mental activity with little action on central and peripheral functions. It is well absorbed orally, metabolized and excreted in urine. 

Limited data are available on the GI absorption of amphetamine in humans. Beckett and Rowland3 reported serum concentrations of amphetamine in two healthy volunteers after a 15-mg oral dose of the D-isomer. Peak serum concentrations of 48 and 40 ng/ml were achieved at 1.25 h when the volunteers urine was acidified. Slightly higher serum concentrations were observed (52 and 47 ng/ml) if the urine pH conditions were not controlled. Rowland4 observed a peak blood concentration of 35 ng/ml, 2 h after a 10-mg oral dose of D-amphetamine to a healthy 66-kg adult. The half-life for the D-isomer was 11 to 13 h compared with a 39% longer half-life for the L-isomer. If the urine were acidified, excretion was enhanced and the half-lives of both isomers were reduced to approximately 7 h.5 Amphetamine demonstrates a linear one-compartment open model over the dose range 20 to 200 mg. 

Amphetamine is metabolized by deamination, oxidation, and hydroxylation. Figure 4.1 illustrates the metabolic scheme for amphetamine. Deamination produces an inactive metabolite, phe-nylacetone, which is further oxidized to benzoic acid and then excreted in urine as hippuric acid and glucuronide conjugates. In addition, amphetamine is also converted to norephedrine by oxidation and then this metabolite and the parent compound are / -hydroxylated. Several metabolites, including norephedrine, its hydroxy metabolite, and hydroxy amphetamine, are pharmacologically active. The excretion of amphetamine depends on urinary pH. In healthy men who were administered 5 mg of isotopically labeled d,l-amphetamine, approximately 90% of the dose was excreted... 

The metabolism of amphetamine has been studied in those presenting with amphetamine psychosis. In the presence of acidified urine, the renal elimination of amphetamine increased significantly. The intensity of the psychosis was found to correlate with the amount of basic polar metabolites excreted in the urine, such as norephedrine and p-hydroxyamphetamine, and not with the plasma amphetamine concentration. This suggests that these metabolites may play an important role in the development of paranoid psychosis in chronic amphetamine users.6... 

In humans, both the d- and L-forms undergo hydroxylation and A-demethylation to their respective />hy dr ox y me thainphetamine and amphetamine metabolites. Amphetamine is the major active metabolite of methamphetamine. Under normal conditions, up to 43% of a D-methamphet-amine dose is excreted unchanged in the urine in the first 24 h and 4 to 7% will be present as amphetamine. In acidic urine, up to 76% is present as parent drug10 compared with 2% under alkaline conditions. Approximately 15% of the dose was present as /7-hydroxymethamphetamine and the remaining minor metabolites were similar to those found after amphetamine administration. Urine concentrations of methamphetamine are typically 0.5 to 4 mg/L after an oral dose of 10 mg. However, methamphetamine and amphetamine urine concentrations vary widely among abusers. Lebish et al.11 reported urine methamphetamine concentrations of 24 to 333 mg/L and amphetamine concentrations of 1 to 90 mg/L in the urine of methamphetamine abusers. 

Nonionized lipid-soluble drugs are resorbed and not eliminated. Generally, drugs that are bases are excreted when the urine is acidic, whereas acidic compounds are excreted in greater quantities if the urine is alkaline. For example, in phenobarbital (weak acid pKa of 7.3) poisoning, alkalinization of the urine with sodium bicarbonate is helpful in eliminating the phenobarbital. In amphetamine toxicity, acidification of the urine with ammonium chloride is required (Figure 1.13). 

Infants born to mothers dependent on amphetamines have an increased risk of premature delivery and low birth weight. The infants may experience symptoms of drug withdrawal. Mothers taking the drug should refrain from nursing, since amphetamine is excreted in human milk. A number of studies using rodents as test animals indicate that women should not take amphetamines when pregnant. 

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