Desmopressin administration route

In this section, the pharmacokinetics of clinically important peptide/protein drugs, such as insulin, EPO, G-CSF, interferon, growth hormone, leuprolide, desmopressin, and antibodies, are described in relation to their administration routes and formulations (i.e., dosage forms). 

Usually, desmopressin is administered intranasally by use of sprays or drops. This administration route of desmopressin was considered to be more efficacious than the oral route, because bypassing the gastrointestinal tract increases the absolute bioavailability from less than 1% to approximately 5%. However, nasal application of desmopressin is accompanied by high intersubject and intrasubject variability in plasma pharmacokinetics [215]. Therefore, there have been several pharmaceutical research efforts to improve nasal delivery of desmopressin. 

The nasal administration was shown to be an effective administration route for lipophilic active substances like fentanyl. Moreover, the nasal route has also been used for the systemic administration of small peptides like buserelin acetate, nafarelin acetate and desmopressin, aU of them containing ten or less amino acid residues. However, for these molecules the nasal route forms only a poor non-invasive alternative to injection, since the nasal bioavailability of these peptides is less than 3-5 %. 

Desmopressin may be given orally, intranasally, SC, or IV. The oral dose must be determined for each individual patient and adjusted according to the patient s response to therapy. When the drug is administered nasally, a nasal tube is used for administration. The nasal tube delivery system comes with a flexible calibrated plastic tube called a rhinyle. The solution is drawn into the rhinyle. One end is inserted into the nostril and the patient (if condition allows) blows the other end to deposit solution deep into the nasal cavity. A nasal spray pump may also be used. Most adults require 0.2 mL daily in two divided doses to control diabetes insipidus. The drug may also be administered via the SC route or direct IV injection. 

Desmopressin, as its acetate salt, is a synthetic analogue of vasopressin in which the N-terminal Cys is devoid of its a-amino function (1-Deamino) and where Arg is present as its D-isomer (D-Arg ), thus the commercial acronym DDAVP (Fig. 7.15). The presence of D-Arg and the absence of the N-terminal amine in the desmopressin structure have increased its half-life such that it is available for oral, parenteral, or nasal use. It is used by all three of these routes of administration to prevent or control polydipsia (excessive thirst), polyuria, and dehydration of patients with diabetes insipidus caused by a deficiency of vasopressin. It also has been approved for the treatment of nocturnal enuresis (bed-wetting), which is believed to be caused by an absence of the normal night time rise in vasopressin levels. 

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