The increase of bone mineral density in the hip was also statistically significant compared to placebo, but only around 1.0% at study endpoint. Continued treatment up to 24 months lead to a continued increase in bone mineral density. Pharmacokinetics
Absorption
Subcutaneous administration of parathyroid hormone into the abdomen produces a rapid increase in plasma parathyroid hormone levels which reach peak at 1 to 2 hours after dosing. The mean half-life is approximately 1.5 hours. The absolute bioavailability of 100 micrograms of Preotact after subcutaneous administration in the abdomen is 55%. Distribution
The volume of distribution at steady-state following intravenous administration is approximately 5.4 liters. Intersubject variability is about 40%. Biotransformation
Parathyroid hormone is efficiently removed from the blood by a receptor-mediated process in the liver and is broken down into smaller peptide fragments. The fragments derived from the amino-terminus are further degraded within the cell while the fragments derived from the carboxy-terminus are released back into the blood and cleared by the kidney. These carboxy-terminal fragments are thought to play a role in the regulation of parathyroid hormone activity. Under normal physiological conditions full-length parathyroid hormone H constitutes only 5-30% of the circulating forms of the molecule, while 70-95% is present as carboxy-terminal fragments. Following administration of Preotact, carboxy-terminal fragments make up about 60-90% of the circulating forms of the molecule. Intersubject variability in systemic clearance is about 15%. Elimination
Parathyroid hormone is metabolised in the liver and to a lesser extent in the kidney. It is not excreted from the body in its intact form.
In clinical studies and postmarketing reports, the side effects seen in 1% or more of the patients were as follows:

Gastrointestinal system: nausea, vomiting, abdominal pain, and diarrhea
Central nervous system: headache
Whole body: fever, phlebitis or thrombophlebitis, complications at the intravenous cannulation site (e.g. induration), unspecified pain, flu-like syndrome, myalgia, chills, and paresthesia
Respiratory: dyspnea
Renal: increased plasma creatinine
Hematological: anemia
Electrolytes: hypokalemia
Liver: increased liver enzymes (asymptomatic)
Hypersensitivity: rash, facial edema, pruritus
Other: tachycardiaAdditionally, infrequent cases of symptomatic liver damage, peripheral edema and swelling, and hypercalcemia have been seen. One case of anaphylaxis (severe allergic reaction) has also been noted. Resistance
Resistance in C. albicans has been described, but is currently still rare. The mechanism is probably a point mutation in the (1→3)-β-D-glucan synthase gene. Drug interactions
Cyclosporin: see under hepatic effects
Tacrolimus: potential pharmacokinetic interactions
Other systemic antimycotic agents: with amphotericin B, itraconazole and mycophenolate, no interactions have been seen
Inducers of drug clearance (e.g. carbamazepine, phenytoin, rifampin, dexamethasone): consider 70 mg intravenous as maintenance dose instead of 50 mg

Duration of treatment
The mean duration of therapy in previous studies was 34 days. Some patients were even healed by a one-day treatment. However, a few patients were treated for as long as 162 days and tolerated the drug well, indicating that longtime use may be indicated and tolerated favourably in complicated cases of aspergillosis. Generally, the duration of treatment is dictated by the severity of the disease, the clinical response, and the improvement of immunocompetence in immunocompromised patients. Dosage
An initial dose of 70 mg by intravenous infusion is given followed by 50 mg intravenous daily.