In one study, the peak levels after a single 50 mg dose of clomifene were 20.37 nmol/L for clomifene, 0.95 nmol/L for 4-hydroxyclomifene, and 1.15 nmol/L for 4-hydroxy-N-desmethylclomifene.Clomifene has an onset of action of 5 to 10 days following course of treatment and an elimination half-life about 5 days. In one study, after a single 50 mg dose of clomifene, the half-life of clomifene was 128 hours (5.3 days), of 4-hydroxyclomifene was 13 hours, and of 4-hydroxy-N-desmethylclomifene was 15 hours. Individuals with the CYP2D6*10 allele showed longer half-lives for 4-hydroxyclomifene and 4-hydroxy-N-desmethylclomifene.Most clomifene metabolism occurs in the liver, where it undergoes enterohepatic recirculation. Clomifene and its metabolites are excreted primarily through feces (42%), and excretion can occur up to 6 weeks after discontinuation. Chemistry
Clomifene is a triphenylethylene derivative. It is a mixture of two geometric isomers, enclomifene ((E)-clomifene) and zuclomifene ((Z)-clomifene). These two isomers have been found to contribute to the mixed estrogenic and antiestrogenic properties of clomifene. History
A team at William S. Merrell Chemical Company led by Frank Palopoli synthesized clomifene in 1956; after its biological activity was confirmed a patent was filed and issued in November 1959. Scientists at Merrell had previously synthesized chlorotrianisene and ethamoxytriphetol. Clomifene was studied in the treatment of advanced breast cancer during the period of 1964 to 1974 and was found to be effective but was abandoned due to concerns about desmosterolosis with extended use. Short-term use (e.g. days to months) did not raise the same concerns however and clomifene continued to be studied for other indications.
The frontal plane QRS is the most helpful clue to distinguish between an ostium secundum ASD and an ostium primum ASD. In primum defects left axis deviation is seen in most patients with an axis of > -30 degrees and very few patients have right axis deviation. In contrast ostium secundum defects have an axis between 0 degrees and 180 degrees with most cases to the right of 100 degrees.In the ECG above, you can see an example of the rSR pattern in V1 with a R greater than S with T wave inversion which is commonly seen in volume overload right ventricular hypertrophy. Diagnosis
Classification
A defect in the ostium primum is occasionally classified as an atrial septal defect, but it is more commonly classified as an atrioventricular septal defect. Treatment
Hemodynamically significant ASDs (flow ratio 1.5:1) are large enough to be closed surgically. The long term prognosis is excellent. Pulmonary hypertension with shunt reversal is a contraindication for surgery, however the pulmonary hypertension can frequently be treated with medicines. The hole can then be closed safely with a good long term prognosis. References
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