The absolute bioavailability of oral melatonin tablets was studied in 12 normal healthy volunteers. Subjects were administered, in a randomized crossover fashion, melatonin 2 mg intravenously and 2 and 4 mg orally. Blood was sampled over approximately eight (estimated) half-lives. Both the 2 and the 4 mg oral dosages showed an absolute bioavailability of approximately 15%. No difference in serum half-life was seen in any of the study phases. Oral melatonin tablets in dosages of 2 and 4 mg show poor absolute bioavailability, either due to poor oral absorption, large first-pass metabolism, or a combination of both. Further studies examining larger doses, in an attempt to saturate first-pass metabolism if it occurs, may be warranted.
A possible mechanism for the photofragmentation of buckminsterfullerene is proposed. The loss of 4,6, 8, ... atoms is found to occur via an "unzipping" process, yielding low-energy structures with 56 to 44 atoms. The significance of 44 and 50 as "magic numbers" can be explained. The loss of only two atoms is a more complex special case.The photofragmentation spectrum of buckminsterfullerene' was reported shortly after the original "discovery" of the species.* It was found that photofragmentation yielded only even numbers of atoms (with 44 and 50 atom clusters favored), which was taken as good evidence that carbon clusters really did form fullerene compounds rather than some other geometry. Subsequently, it has been discovmd that endohedral metal ions, such as La3+, can be "shrink-wrapped'' by sequentially removing pairs of atoms, in which case 44 atoms also seem to be magic.3 In this Letter we suggest a mechanism by which buckyball can fragment to as small as 44 atoms, which accounts for much of the experimental data, including magic numbers, and which does not require breaking as many bonds as methods previously proposed.'In 1986 Stone and Wales suggested a process by which buckyball can isomerize to a structure in which two pentagons are nearest neighbors (defect b~ckyball).~ It has recently been reported that this isomer is not much higher in energy than pure buckyball, and the reason why it has yet to be observed probably stems from kinetic rather than thermodynamic effect^.^ O'Brien et al. ' have proposed a mechanism by which defect buckyball could "unzip*, sequentially removing 2,4, or 6 atoms, but given that the defect form has never been experimentally ~bserved,~ perhaps this is not a plausible mechanism. On the other hand, Stanton6 has done an extensive study of the energetics of the mechanism propaped by O'Brien et al. and illustrates that it is consistent with experiment.Recently, Liu et ala7 published an algorithm by which all fullerene isomers can be generated. They define two variables:p represents the number of pentagon-pentagon edges, and q denotes the number of pentagon-pentagon-pentagon vertices. The algorithm requires p and q as input parameters, thus constraining possible structures. Since p and q have obvious chemical significance, the ability to choose constraints in advance has advantages. Second, Liu et al.'s method depends on the appropriate choice of a seed, i.e., a small system of hexagons and pentagons from which the structures are generated. If the goal is to find all possible structures, then the seed should be as small as possible so as to ensure all structures are generated. But our application is different: we want to find h"s of Cs8, c 5 6 , Cs4, etc., which are as close as possible to the original buckyball. Thus, we start with the largest possible buckyball fragment from which the above isomers can be generated, and we require that the resulting isomer contain the smallat possible values for p and q.Recently, Lyons et ala8 have studied isomers of CU using a many-body classical...
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