Drug availability

As a practical result there are now at least six synthetic anti-malarial drugs available to malariologists, including the three pre-war drugs, pamaquln, mepacrine and plasmocide. 

Miltefosin The antileishmanial activity of this anticancer drug was discovered in the mid-1980s. It is the first oral drug available to treat visceral and cutaneous/mucocutaeous leishmaniasis. However, the registration process is slow. 

Amphotericin B is the most effective drug available for die treatment of most systemic fungal infections. Administration often results in serious reactions,... 

The antiviral strategies discussed earlier as well as all antiviral drugs available to date are based on the principles of conventional chemotherapy. However, recent discoveries and developments in molecular biology have opened perspectives for alternative approaches of intervention. 

The stimulant urge-impulses are seusitive to euviroumeutal cues such as retumiug home aud associated multiple situatioual stimuli (e.g., paraphernalia, friends, etc.). With continued drug availability, it is not unusual to observe repetitious cycles of bingeing with intervening crash and intermediate withdrawal phases over a period of months. It is noted that conditioned withdrawal responses are less pronounced than with opiates yet, withdrawal appears to have a phase-specific relation to the reemergence of cue-sensitive responses that deserves further research. 

The impact of presystemic elimination may be clearly understood by considering the following relationships among the several steps involved in making the drug available to the systemic circulation. The significance of this relationship is its multiplicative nature, since most of the processes are sequential. These relationships assume linear or first-order kinetics (i.e., there is no nonlinearity or saturation effects). 

Factors Influencing Drug Absorption and Drug Availability... 

VI. PHYSICOCHEMICAL VERSUS BIOCHEMICAL FACTORS INFLUENCING DRUG ABSORPTION AND DRUG AVAILABILITY... 

As described in Chapter 2, the extent of oral drug availability (Eoral) may be described as the product of absorption availability (Fabs), the extent of availability through the gastrointestinal membranes (FG), and the availability through the liver (F/f) ... 

As mentioned earlier in this chapter, penicillins are very unstable in aqueous solution by virtue of hydrolysis of the p-lactam ring. A successful method of stabilizing penicillins in liquid dosage forms is to prepare their insoluble salts and formulate them in suspensions. The reduced solubility of the drug in a suspension decreases the amount of drug available for hydrolysis. An example of improved stability of a... 

A second factor reducing drug availability is the drainage associated with hydrodynamic flow of tears through the precorneal space and cul-de-sac, discussed above. A third and more difficult problem for delivery by nondirectional technologies and devices is the undesirable adsorption and absorption by nearby noncorneal tissues competing for therapeutic agents. 

An improvement in this system is to coat the ion-exchange resin with a hydrophobic rate-limiting polymer, such as ethylcellulose or wax [43], These systems rely on the polymer coat to govern the rate of drug availability. 

B. Hoener and L. Z. Benet, Factors influencing drug absorption and drug availability, in Modern Pharmaceutics (G. S. Banker and C. T. Rhodes, eds.), Marcel Dekker, New York, 1979, pp. 143-182. 

The coupling of solute transport in the GI lumen with solute lumenal metabolism (homogeneous reaction) and membrane metabolism (heterogeneous reaction) has been discussed by Sinko et al. [54] and is more generally treated in Cussler s text [55], At the cellular level, solute metabolism can occur at the mucosal membrane, in the enterocyte cytosol, and in the endoplasmic reticulum (or microsomal compartment). For peptide drugs, the extent of hydrolysis by lumenal and membrane-bound peptidases reduces drug availability for intestinal absorption [56], Preferential hydrolysis (metabolic specificity) has been targeted for reconversion... 

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