Blood concentration

Doses range from 6 to 33 ppm ia the diet, but very htde if any ionophore can be measured ia the circulation after feeding. Monensia is absorbed from the gut, metabolized by the Hver, and excreted iato the bile and back iato the gut. Thus tissue and blood concentrations are very low. Over 20 metabohtes of monensia, which have Htde or ao biological activity, have beea ideatified (47,55). 

Some tablets that provide a sustained period (up to 8—12 h) of therapy may be coated during processing. A portion is released first to bring the dmg to the desired blood concentration (onset of activity), whereas a sustained-release portion maintains an effective level for a prolonged period of time (duration of activity), eg, by coating erosion or diffusion of dmg through it. 

Delayed action soHd products are designed like conventional dosage forms to release all their dmg contents at one time, but only after a delayed period. Thus, the duration of action and the blood concentration—time curve is like that of a conventional product. However, the onset time is purposely designed to be long. 

Saponins. Although the hypocholesterolemic activity of saponins has been known since the 1950s, thek low potency and difficult purification sparked Htde interest in natural saponins as hypolipidemic agents. Synthetic steroids (292, 293) that are structurally related to saponins have been shown to lower plasma cholesterol in a variety of different species (252). Steroid (292) is designated CP-88,818 [99759-19-0]. The hypocholesterolemic agent CP-148,623 [150332-35-7] (293) is not absorbed into the systemic ckculation and does not inhibit enzymes involved in cholesterol synthesis, release, or uptake. Rather, (293) specifically inhibits cholesterol absorption into the intestinal mucosa (253). As of late 1996, CP-148,623 is in clinical trials as an agent that lowers blood concentrations of cholesterol (254). 

Certain vertebrates have an astonishing ability to accumulate vanadium in their blood. For example, the ascidian seaworm Phallusia mammilata has a blood concentration of V up to 1900 ppm, which represents more than a millionfold concentration with respect to the sea-water in which it lives. The related organism Ascidia nigra has an even more spectacular accumulation with concentrations up to 1.45% V (i.e. 14 500 ppm) in its blood cells, which also contain considerable concentrations of sulfuric acid (pH 0). One possibility that has been mooted is that the ascidia accumulates vanadate and polyvanadate ions in mistake for phosphate and polyphosphates (p. 528). 

Alcohol dehydrogenase is a cytoplasmic enzyme mainly found in the liver, but also in the stomach. The enzyme accomplishes the first step of ethanol metabolism, oxidation to acetaldehyde, which is further metabolized by aldehyde dehydrogenase. Quantitatively, the oxidation of ethanol is more or less independent of the blood concentration and constant with time, i.e. it follows zero-order kinetics (pharmacokinetics). On average, a 70-kg person oxidizes about 10 ml of ethanol per hour. 

Dtug interactions can cause serious problems in clinical practice especially when the affected dmg has the potential to be highly toxic. Furthermore, pharmacokinetic interactions are clinically important if the affected dmg has a narrow therapeutic range (i.e. small difference between the minimum effective concentration and the toxic concentration Fig. 1) and a steep concentration-response curve (i.e. significant alterations in pharmacological and/or adverse effects caused by small changes in blood concentration). 

It is important to monitor closely serum blood levels of chloramphenicol, particularly in patients with impaired liver or kidney function or when administering chloramphenicol with other drugs metabolized by the liver. Blood concentration levels exceeding 25 mcg/mL increase the risk of the patient developing bone marrow depression. 

Shi J, Hui L, Xu Y, et al Sequence variations in the mu-opioid receptor gene (OPRM1) associated with human addiction to heroin. Hum Mutat 19 459 60, 2002 Shinderman M, Maxwell S, Brawand-Arney M, etal Cytochrome P4503A4 metabolic activity, methadone blood concentrations, and methadone doses. Drug Alcohol Dependence 69 205-211, 2003... 

Little is known regarding the pharmacokinetic properties of volatile nitrites in humans, particularly isobutyl nitrite and its primary metabolite, isobutyl alcohol. In rodents, after an intravenous infusion of isobutyl nitrite, blood concentrations peaked rapidly and then declined, with a half-life of 1.4 minutes and blood clearance rate of 2.9 L/min/kg (Kielbasa and Fung 2000). Approximately 98% of isobutyl nitrite is metabolized rapidly to isobutyl alcohol, concentrations of which also decline rapidly, with a half-life of 5.3 minutes. Bioavailability of inhaled isobutyl nitrite at a concentration of 300-900 ppm is estimated to be 43%. 

There are very limited studies on absorption of organotins. Noland et al. (1983) formd maximum blood concentrations of dimethyltin after dosing pregnant rats... 

Water-soluble products of digestion are transported directly to the fiver via the hepatic portal vein. The fiver regulates die blood concentrations of glucose and amino acids. 

Experiments demonstrate that oral absorption of trichloroethylene in animals is extensive and metabolism is rapid. A study of F344 rats which were fasted for 8 hours prior to oral dosing by gavage found a rapid appearance of trichloroethylene in the blood which peaked after 0.75 hours, while the peak concentrations of the metabolites trichloroethanol and TCA occurred at 2.5 and 12 hours, respectively (Templin et al. 1995). The same investigators also dosed beagle dogs and found that blood concentrations of trichloroethylene, trichloroethanol, and TCA peaked after 1, 2.5, and 24 hours, respectively. In both species, TCA concentration did not peak until well after the trichloroethylene concentration in blood was below detectable levels (Templin et al. 1995). 

This model accurately predicted the time curves for blood concentration and urinary excretion of metabolites by male volunteers exposed to 100 ppm trichloroethylene (Sato et al. 1991). It was found that, while the amount of metabolite excretion increases with body weight, the concentration does not, because of a corresponding increase in urinary volume. Also, women and obese people, compared with slim men, have lower concentrations but longer residence times of blood trichloroethylene because of their higher fat content (Sato et al. 1991). As a consequence, the model predicted that 16 hours after exposure to trichloroethylene, one could expect a woman s blood level to be 30% higher and an obese man s level to be twofold higher than that of a slim man (Sato 1993). 

Kishi R, Harabuchi 1, Ikeda T, et al. 1993. Acute effects of trichloroethylene on blood concentrations and performance decrements in rats and their relevance to humans. Br J Ind Med 50 470-480. 

Cyclosporine and tacrolimus are calcineurin inhibitors that are administered as part of immunosuppressive regimens in kidney, liver, heart, lung, and bone marrow transplant recipients. In addition, they are used in autoimmune disorders such as psoriasis and multiple sclerosis. The pathophysiologic mechanism for ARF is renal vascular vasoconstriction.41 It often occurs within the first 6 to 12 months of treatment, and can be reversible with dose reduction or drug discontinuation. Risk factors include high dose, elevated trough blood concentrations, increased age, and concomitant therapy with other nephrotoxic drugs.41 Cyclosporine and tacrolimus are extensively metabolized by... 

Dopamine agonists are useful as initial therapy, as they can delay the need to start levodopa and can decrease the risk of developing motor fluctuations by two- to threefold during the first 4 to 5 years of treatment. After a few years, dopamine agonists inadequately control the patient s symptoms and levodopa needs to be started. In advanced disease, dopamine agonists can be added to levodopa because they have a longer duration of action, minimize fluctuations in dopamine blood concentrations, decrease off-time, improve wearing-off symptoms, allow a reduction in levodopa dose, and improve ADLs.1-3,16,22,23,26... 

Patients with severe dyskinesias and off periods may achieve more constant blood concentrations (lower peak and higher trough concentrations) by taking a liquid formulation of levodopa with carbidopa. Each day patients make a 1 mg/mL levodopa... 

Disulfiram inhibits CYP1A2, resulting in an increase in theophylline blood levels monitor theophylline blood concentration may need to decrease theophylline dose. 

---