1The pharmacokinetics and pharmacodynamics of intranasal (IN) and oral 1‐deamino‐8‐d‐arginine vasopressin (DDAVP) were compared in 10 Chinese adults with central diabetes insipidus previously controlled on IN DDAVP. This was followed by comparison of the acute pharmacodynamics of commonly used oral preparations (containing 100, 200 and 400 μg per tablet) and a 1 year prospective evaluation of the long‐term safety and efficacy of oral DDAVP.
2Following 20 μg IN and 200 μg orally, respective plasma DDAVP concentrations peaked after 45.6±7.3 and 93.3±3.3 (mean±s.e.mean) min, reaching 24.1±4.7 and 15.1±3.2 pmol l−1 and respective terminal half‐lives were 2.2±0.1 and 2.0±0.1 h. Based on the area under the concentration‐time‐curve, the bioequivalent IN/oral ratio was 1:16.
3As judged by changes in urine flow rate and osmolality after IN or oral (100, 200 or 400 μg) DDAVP, antidiuretic activity increased rapidly during the second hour and peaked at 4 h. The antidiuresis duration and magnitude correlated with the oral dose (P<0.001 and <0.05 respectively), and was least following 100 μg (P<0.01 vs 200 or 400 μg). Increasing the dose from 200 to 400 μg did not increase maximal antidiuretic activity significantly, but there was a trend towards a longer duration of action (P=0.076).
4During the 1‐year prospective study with oral DDAVP 300–600 μg per day in two to three doses, stable and satisfactory antidiuresis (comparable with that on previous IN therapy) was maintained; tablets were well‐tolerated and no side‐effect warranted drug withdrawal.
5These findings suggest that the 100 and 200 μg preparations of oral DDAVP are adequate for the long‐term control of central diabetes insipidus in our population, and that the 400 μg preparation may have a role if the frequency of administration is to be reduced.
Hepatoid carcinomas are uncommon extra-hepatic neoplasms exhibiting features of hepatocellular carcinoma and they are most frequently described in the stomach. We report a 64-year-old woman with a malignant insulinoma showing focal hepatoid differentiation and biochemical evidence of alpha-fetoprotein (AFP) production. The current case is the first malignant insulinoma with hepatoid differentiation. Resection of the primary tumor followed by regional embolization was peformed. The patient died 22 months after initial presentation. Thus, the presence of hepatoid differentiation in pancreatic tumor should be noted as the tumor may be associated with elevated AFP. The features of pancreatic hepatoid carcinomas are discussed.
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