Oral drug administration proteins

Allopurinol is largely absorbed after oral ingestion, reaching peak blood levels in about 1 hour. In contrast to the uricosuric drugs, allopurinol is not appreciably bound to plasma proteins and is only a minor substrate for renal secretory mechanisms. The formation of oxypurinol and the finding that this metabolite is in part actively reabsorbed in the proximal tubule account for the long half-life of the metabolite (18-20 hours) and permits once-a-day drug administration. 

Oral drug absorption is nearly complete and concomitant administration of food may decrease the rate, but not the extent of absorption. The drug is 99% bound to plasma proteins and metabolised (1 to 3% of a dose is excreted unchanged in the urine) to several metabolites which are excreted mainly in the urine or the faeces. 

Cefaclor is well absorbed after oral administration. The presence of food may delay the absorption of cefaclor but the total amount absorbed remains unchanged. About 25 percent of the drug is protein bound. Cefaclor is widely distributed in the body. It is rapidly excreted by the kidneys, up to 85% appears unchanged in the urine within two hours. 

Hydrophobic polymers are often used to deliver biomacromolecules regardless of the route of administration. The rapid transit time of approximately 8 hours limits the time of a device in the gastrointestinal (GI) system, consequently the mechanisms possible for oral drug release are limited. The predominant method of release from hydrophobic polymers has been degradation, or biodegradation, of a polymeric matrix by hydrolysis (Figure 11.1). In fact, all of the hydrophobic polymers described in this chapter for use as oral protein or peptide delivery are hydrolytically unstable. 

In the past two decades, many studies have tested adjuvants that act by either permeabilizing the rectal mucosa or inhibiting drug degradation. Oral and rectal routes of drug administration are unsuitable for adequate absorption of various compounds with a peptide or protein structure and of several hydrophilic antibiotics. The use of absorption enhancers, e.g., salicylates, enamines, surfactants, and straight-chain fatty acids, has gained wide interest... 

Oral administration is the most common route of drug administration. Major physiologic processes in the GI system include secretion, digestion, and absorption. Secretion includes the transport of fluid, electrolytes, peptides, and proteins into the lumen of the alimentary canal. Enzymes in saliva and pancreatic secretions are involved in the digestion of carbohydrates and proteins. Other secretions such as mucus protect the linings of the lumen of the GI tract. Digestion is the breakdown of food constituents into smaller structures in preparation for absorption. Both drug and food constituents are mostly absorbed in the proximal area (duodenum) of the small intestinal. The process of absorption is the entry of constituents from the lumen of the gut into the body. Absorption may be considered as the net result of both lumen-to-blood and blood-to-lumen transport movements. 

One of the key pieces to development of a successful drug product is the ability to deliver the drug to the site of action with minimal discomfort or inconvenience to the patient. For small molecule therapeutics, there is a wide range of options available for drug administration. Delivery via injection (IV, IM, and SC), oral, nasal, ocular, transmucosal (buccal, vaginal, and rectal), and transdermal routes is possible with small molecule drugs. However, the size of proteins and the complexity of their structures severely limit the routes of administration available to proteins. 

Although routine oral delivery of proteins has not been realized, some protein formulations have been developed for pulmonary delivery. Pulmonary delivery can result in either parenteral or local administration of the drug and, like oral delivery, is considered non-invasive. As with other routes of delivery, the size of the protein may limit its ability to be delivered systemi-cally via the pulmonary route of administration. Pulmozyme , a DNase-based formulation approved for the treatment of cystic fibrosis (CF), is delivered to the lungs by a nebulizer to clear blockage of the airways in the CF patient.Formulations for insulin to be administered by inhalation for systemic delivery of... 

After oral administration, carbamazepine is slowly but erratically absorbed with wide individual variability. Over 80% of the drug is protein bound.. The elimination half-life early in therapy is approximately 24 hours. With chronic therapy, the enzyme cytochrome P450 3A4 (CyP 3A4) and its associated drug transporter P-glycoprotein (Pg)— responsible for metabolism— are induced, and the elimination half-life is reduced to 15 to 20 hours. Because hepatic metabolism is the principal means by which plasma concentration is reduced, any reduction in liver function results in drug accumulation. 

Sodium phenylbutyrate (NaPB), a Food and Drug Administration-approved oral medication for hyperammonemia, induces astrocytic BDNF and NT-3 expression via the protein kinase C (PKC)-cAMP-response element-binding protein (CREB) pathway. NaPB treatment increased the direct association between PKC and CREB followed by phosphorylation of CREB (Ser133) and induction of DNA binding and transcriptional activation of CREB. NaPB increased the levels of BDNF and NT-3 in the CNS and improved spatial learning and memory in a mouse model of AD [560],... 

---