Extent of Drug Use

In 1986, the animal drug market was estimated to be worth over 9000 million, with feed additives and therapeutics each contributing 45% of the total (6). The United States shared 28% of the market, and Western Europe 24.5%. A breakdown by animal usage showed that cattle formed 32%, with poultry making up 24%, swine 21%, sheep 10% and horses 4%. 

After the United States, Japan is the second largest consumer of animal health products. In 1990, 110 feed additives were approved for use in Japan and production reached 78,000 tons estimated to be worth 60,000 million yen. 

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The extent of drug use in 2003 for different drugs is presented in Table 4.1. According to the 2003 National Survey on Drug Use and Health (NSDUH), 11.2% of 12- to 17-year-olds reported current use of illicit drugs, 30.5% reported use at least once during their lifetime, and 21.8% reported use within the pastyear. ... 

Extent of drug use (annual prevalence ) estimates 2005/6 (or latest year available)... 

Reuschel and Smith conducted a study in which they measured the concentration of benzoylecgonine in black, brown, blond, and red hair collected from jail detainees. They tested 48 hair samples for drug and 22 tested positive. The concentration of benzoylecgonine in black and brown hair was 5.6 + 5.2 ng/mg of hair in comparison to that in blond and red hair, which was 1.39+ 1.34 ng/mg of hair. However, Reuschel and Smith did not elicit information about prior drug use from individuals, and these results could be attributable to differences in the frequency and extent of drug use. 

The CAT model estimates not only the extent of drug absorption, but also the rate of drug absorption that makes it possible to couple the CAT model to pharmacokinetic models to estimate plasma concentration profiles. The CAT model has been used to estimate the rate of absorption for saturable and region-depen-dent drugs, such as cefatrizine [67], In this case, the model simultaneously considers passive diffusion, saturable absorption, GI degradation, and transit. The mass balance equation, Eq. (51), needs to be rewritten to include all these processes ... 

In our own studies to establish an in-house correlation between Caco-2 permeability and extent of drug absorption in humans, a set of 25 model drugs was used (Table 5.1). The importance of concentration and pH conditions were investigated and transport was studied both in apical to basolateral (absorptive) and basolateral to apical (secretory) directions. The apparent permeability coefficients were determined at concentrations of 10, 50, and 500 pM, and at two different settings of apical/basolateral pH values 6.5/7.4 and 7.4/7.4. The marker compounds represented a good diversity in molecular structure and transport properties and covered a range of low (<20%), moderate (20-80%) and high (>80%) extent of absorption in humans (Tab. 5.1). 

Lennernas s group at Uppsala has performed extensive studies to confirm the validity of this in vivo experimental set-up at assessing the rate and the extent of drug absorption. Recovery of PEG 4000 (a non-absorbable marker) is more than 95%, which indicates that the absorption barrier is intact. In addition, maintenance of functional viability of the mucosa during perfusion has been demonstrated by the rapid transmucosal transport of D-glucose and L-leucine. Estimation of absorption half-lives from the measured Pefr agree well with half-lives derived from oral dose studies in humans (i.e. physiologically realistic half-lives). Human Peff estimates are well correlated with the fraction absorbed in humans, and served as the basis for BCS development, and hence the technique is ultimately the benchmark by which other in situ intestinal perfusion techniques are compared. The model has been extensively used to... 

Automated pharmacy services as they exist in several European countries also facilitate the study of drug use to a considerable extent. 

Studies using smaller implants of 2.9 mm diameter indicated statistically significant differences in the two rate constants (Table 2) and extent of drug released from the implant in comparison with implants of mean diameter 6.2 mm. This could be attributed to an increase in surface area per unit volume of the smaller implant. 

The permeability class boundary is based indirectly on the extent of absorption (fraction of dose absorbed, not systemic BA) of a drug substance in humans and directly on measurements of the rate of mass transfer across human intestinal membrane. Alternatively, nonhuman systems capable of predicting the extent of drug absorption in humans can be used (e.g., in vitro epithelial cell culture methods). In the absence of evidence suggesting instability in the gastrointestinal tract, a drug substance is considered to be highly permeable when the extent of absorption in humans is determined to be 90% or more of an administered dose based on a mass balance determination or in comparison to an intravenous reference dose. 

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