Regional Drug Administration

GaUo et al. [65] applied a physiologically-based pharmacokinetic model to the targeting of anti-cancer drugs to the brain following intra-arterial administration in gUoma-2 bearing rats. 

Malhotra et al. [66] modelled the route of administration-based enhancement of delivery of EAB 515, a hydrophilic N-methyl-D-aspartate antagonist, to the brain. 

Stevens et al. [55] determined the relationship between the DTI and pharmacokinetic parameters of three non-steroidal anti-inflammatory drngs nsing the rat air ponch inflammation model. The derivation of the DTI was modified to take into account the simnltaneons influx of plasma albumin, to which the drugs were extensively bonnd. 

PK/PD evaluation of pnhnonary administration has been described in several papers by Hochhaus et al. [67,68]. 

---

Interferon-a2b has diverse mechanisms of action, including antiviral activity, impact on cellular metabolism and differentiation, and antitumor activity.42 The antitumor activity is due to a combination of direct antiproliferative effect on tumor cells and indirect immune-mediated effects.42 Interferon-a2b is currently approved by the Food and Drug Administration (FDA) as adjuvant therapy for patients who are free of disease after curative surgical resection but are at high risk of MM recurrence. This includes patients with bulky disease or regional lymph node involvement such as stage IIB, IIC, or III disease.43 It is controversial if interferon-a2b (IFN) should be offered as adjuvant therapy for every high-risk MM patient. The reason is because clinical trials with different doses of IFN have not proved definitively that IFN improves overall patient survival. 

Notwithstanding the plaints above, the last question must be discussed can a delivery system be used to overcome conditions imposed by the biological system (excluding those posed by the route of administration) to achieve optimized therapy Two major approaches to this end have been proposed regional drug delivery and targeted drug delivery. 

Fomivirsen (Vitravene), an anti-CMV agent, is the first antisense oligonucleotide to be approved by the U. S. Food and Drug Administration (FDA) as an antiviral therapy. Fomivirsen is an oligonucleotide complementary to the major immediate early region 2 (IE2) of CMV mRNA. By binding to IE2 mRNA, fomivirsen prevents its translation to protein and thereby blocks viral replication. Because this mechanism of action is... 

Since blood levels are lowered up to 30% when vasoconstrictors are added to local anesthetics, localized neuronal uptake is enhanced because of higher local tissue concentrations in the region of drug administration, and the risks of systemic toxic effects are reduced. Furthermore, when used in spinal anesthesia, epinephrine acts directly on the cord to both enhance and prolong local anesthetic-induced spinal anesthesia by acting on a2 adrenoceptors, which inhibit release of... 

---