Absorption rate and extent

The data presented above suggest that methyl parathion would be absorbed by humans following ingestion of food and drinking water contaminated with methyl parathion. However, no data are available on the rate and extent of absorption in humans. 

Absorption, Distribution, Metabolism, and Excretion. Evidence of absorption comes from the occurrence of toxic effects following exposure to methyl parathion by all three routes (Fazekas 1971 Miyamoto et al. 1963b Nemec et al. 1968 Skiimer and Kilgore 1982b). These data indicate that the compound is absorbed by both humans and animals. No information is available to assess the relative rates and extent of absorption following inhalation and dermal exposure in humans or inhalation in animals. A dermal study in rats indicates that methyl parathion is rapidly absorbed through the skin (Abu-Qare et al. 2000). Additional data further indicate that methyl parathion is absorbed extensively and rapidly in humans and animals via oral and dermal routes of exposure (Braeckman et al. 1983 Flollingworth et al. 1967 Ware et al. 1973). However, additional toxicokinetic studies are needed to elucidate or further examine the efficiency and kinetics of absorption by all three exposure routes. 

A complication here, however, is noted with those drugs that exhibit a limited chemical stability in either acidic or alkaline fluids. Since the rate and extent of degradation is directly dependent on the concentration of drug in solution, an attempt is often made to retard dissolution in the fluid where degradation is seen. There are preparations of various salts or esters of drugs (e.g., erythromycin) that do not dissolve in gastric fluid and thus are not degraded there but which dissolve in intestinal fluid prior to absorption. A wide variety of chemical derivatives are used for such purposes. 

Rectal Administration. The administration of drugs by a solid rectal dosage form (i.e., suppositories) results in a wide variability in the rate and extent of absorption in children [79]. This fact, coupled with the inflexibility of a fixed dose, makes this a route that should not be promoted for pediatric patients. At least one death involving a 7-month-old infant can be directly attributed to the use of solid rectal dosage form of a therapeutic dose of morphine [80]. 

The rate and extent of intestinal absorption of cimetidine has been widely discussed previously, and a reasonable value of fa for this drug has been estimated as 75% [90, 91]. It has been reported that cimetidine is a substrate for both P-gp and/ or organic cation transporters (OCNT1 and OCNT2) [82, 92]. We determined the... 

Solubility, dissolution rate, and intestinal permeability, are the major bio-pharmaceutic factors that affect the rate and extent of absorption of an oral drug product. Particularly for water insoluble drugs that have generally high membrane permeability (BCS Class II), dissolution, and dose are the most critical factors affecting the rate and the extent of oral absorption. 

P. Langguth, K. M. Lee, H. Spahn-Langguth, G. L. Amidon. Variable gastric emptying and discontinuities in drug absorption profiles dependence of rates and extent of cimeti-dine absorption on motility phase and pH. Biopharm. Drug Disposit. 1994,... 

Oral bioavailability of a drug is primarily dependent upon its rate and extent of drug absorption and systemic clearance. Systemic clearance is primarily composed of hepatic, renal and biliary clearance. The PK properties are in turn directly impacted by the drug s physical properties, such as, log P, log D and pKa. The physical properties are in turn a function of the compound s structure, molecular weight, number of hydrogen bond donors and acceptors, and number of rotatable bonds. Oral bioavailability is the outcome from the dynamic interplay of these factors in the biological system. 

IM diazepam and chlordiazepoxide should be avoided because of variability in rate and extent of absorption. IM lorazepam provides rapid and complete absorption. 

Figure 2-1 Toxic blood level concentration as a function of route of exposure. Wide variations are expected as a result of rate and extent of absorption, distribution, biotransformation, and excretion.

Studies using the inhalation route might be useful to determine the potential human health risk in populations that may be occupationally exposed to hexachloroethane vapors for long periods. Additional chronic oral studies may be useful to help further clarify the dose-response relationships and better characterize thresholds. Studies by the dermal route would not be useful until the rate and extent of absorption have been better characterized. 

Because they are crucial to the course of an organism s response, the rate and extent of absorption of biologically active agents from the GI tract also have major implications for the formulation of test material dosages and also for how production (commercial) materials may be formulated to minimize potential accidental intoxications while maximizing the therapeutic profile. 

Maximum plasma concentration, CmaK, is a measure of both the rate and extent of drug absorption. It is also an essential component of the bioavailability... 

When the rate and extent of absorption of two drugs are different, they are not considered as equivalent products. When the rate and extent of absorption of two products are equal, they are considered equivalent. In some special cases where rate of absorption is different but the extent is same, the products are considered equivalent. 

No studies were located regarding the toxicokinetics of di-/ -octylphthalate in humans or animals following inhalation or dermal exposure. Information on the toxicokinetics of 6i-n-octylphthalate in humans following oral exposure is not available. There are studies that provide indirect evidence for the oral absorption of di- -octylphthalate in animals (Albro and Moore 1974 Oishi 1990 Poon et al. 1995) however, quantitative information is lacking on the rate and extent of absorption following oral exposure to di- -octylphthalate. Information on the distribution of di-w-octylphthalate is limited to oral studies in rats by Oishi (1990), which reported the identification of mono- -octy lphthalate in blood and testes within 1-24 hours (plasma peak at 3 hours, testes peak at 6 hours) after dosing, and by Poon et al. (1995), which reported di- -octylphthalate... 

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