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HlRUDIH J.S. narLA m =l-1 1M THE ELDERLY PWARMAOOKINElKSOEPJDFQIPINE:GTZSAFIERSINGLE de 1 a R ~ ~ ~ o N. DOSE u AND ATSlEADYflA'IE S , W HltiAL'IHYEIDERLY AND &pt. of^^ H-J. RBthig* WUI H. 6riitschc YOUNG S- State Phamcology, University of the Orange Free yest-ie#loct.f~ntein .any. and W h s t A6, Frankfurt, Ten hea study tjth~, elderl~ v~lunteers participated in a investigate tbe effect of ageing on the phamco$inetics of hirudin. A si l= dose of 0.1 z:: $p administered intravmouqy; blood md pens were collected sequential ly, hirudin tisle (pponcentratims and partial throllboplastin T) of blood ere measured in all specilens. cobeentrations and creatiniae were aeasured in the urine. Safety phatnacalogy - clinical chm'stlJI, haematology and urinalysis - was per- foe* A conparison uas aade between the phar- mcok'ne\ics of hirudin in the elderly and in ywng hunteers receiving 0.1, 0.35 and 0.5 .g/kg hirudin z .. -;kT1c VARUBtES The loaxib hirudin plasma concentration was 668 ng/ g ! 499 - 860 &8l) and was observed at e area \rtrder the plasma coacentration ti.e cUwe wat 715 ng.h/ml. This was between 10 and 34% h!gher than the mean values of the young volunteers, with comespondiag lower total clearance. The total ti* and total volume of distribution for the 0 - 5h PWod were about 35% and 8% respectively, higher than for young volunteers. The .can urinary recovery of hirudin for the elderly was almost 20% less thaq for the young ,volunteers. kan ren;il clearance of 61.8 ml/8in of the elderly volunteeh was about 40% lower than that of the young v01 unteers . mLwIon Hirudin was tolerated well. Both total body clearance and renal clearance were lower in the elderly group than in young volunteers. There was a good correl at i on between creat ini ne clearance and total body clearance. Dosing may have to be adapted in accordance with creatfnine clearance when large doses are given to elder1 y patients. - ~ - A l q E w ~ m r r r a D r o a T m ~ o a r Hc ~arnard*, JB Itruger. Departrent of Chaical Pathology, 11OPS, PO Box 339, Bloerfcmtein 9300. a r ~ The presented here displays goad reeoluticm of all d, less baseline noise than the misting ,U and bars the dvautage of separating B-carotem frost intm5ering peeks lib retin01 etearate. Tbe ,- is able to differentiate betveen cis ad trans iso-s ~f B-carotene and the analytical procedure has a the spau of 15 minutes. GGroenetvoud8,HGLuue,FO~, MvooDykHKLEtuadL Department~.UOF$POBonU9(G6X~ 2Althougharnlnnllntinaof~nifedipimdoesooouwhenadministered onm daily, it is WY of no clinical relePpace. THE INFLUENCE OF INTRAGASTIUC- AND URINE -pH MAMPUUTK)NONFUROSEMLDEKINEllCSANDDYNAMI~ INHEALTBY-
624 SAMJ VOL. 80 7 DES 1991 A SENSlTlVE HPU: METHOD FOR TFIE DETERMI[NATION OF MAPROTIUNEJNPLASMA IN VNOANnTaOMBOTEESEEFFEKTEVANLOgALEVERSUS SISTEMIESE TERAPIE MET STERg ANTAGONISIE VAN TROMBIEN HF Ib ' A Lumsden, LA Harker, SR Hanson. Departement Hemak?gie, UOVS, Bloedomdn en Afdekg Hematolog..e/Onkalogie, Emory Universiteit, Atlanta, Ga. Trombien sDeel 'n sleutekol in arteriE1e trombose. en daar is verskeie sterk, 60tegnologies-ontwikkelde antitrombie&iddels wat h-on Maprotiline is a tetracyclic anti&pressant drug drug in the thetreatment of a variety of depressive states and other psychiatric disorders. Although a number of HPLC methods have been published for the stalling en vlaatiiefunksie inbier. Hierdie studie ver~elvk die Iokale determinationof maprotiline in plasma, it did not fulfill our needs since versus-sistkmi& antitrombotiese effekte van rekomb'i&te hirudin, we needed a sensitive method for the determination of low plaqm DPhe-Pro-Arg-chlorom&el ketoon @FPRCHfl) en heparien op concentrations of maprotiline in a bioavailability trial The volunteers plaatjie-neerllegging (PN) op trombogeniese Dacron vaskuI€re received only 75mg of maprotiline since higher dosages caused severe prosteses (05 m?. Die pr0Stese.s is in silikombberbuise (4 mm id) adverse effects. ingebou en as ver1engstukke in permanente kmorale arteriweneuse Aim fistels in bobbejane e laas In 12 kontrole studies het PN (gemeet as die neerlegging vanqSh-kmerkte plaatjies met h sidikekamera) Our aim was therefore to develop a sensitive method for the determi- 'n maksirmrm van 2,1+0,3 X 109 plaatjies neergele na 2,S nur bereik nation of low concentrations of maprotiline in plasma PN het dan afgeneem na 1,8?0,3 X 19 plaatjies na 4 uur. In alle Method studies waar die diere behandel is, is 'n trombus toegelaat om vir 15 Fromplasma, maprotiline and the internal standard nortriptyline, were minute op die prostese te vorm v&rdat daar met beh&eling begin is. extracted with diethvlether. 'Ihe omanic laver, transferred to a clean Sistemiese behandelim met r-hirudin (20 nmd/k~-mid en D ampoule was evapokted to dryness-and thk residue derivatized with FPRCHZCl (100 nmol/&nin) het PN tydek -infusik Nadat ' ' daosyi chloride by leaving it in the dark at room temperature for 30 min. die behandeling gestaak is, is plaatjies weer neergelk M PN Proline was added to remove the- dansyl chloride and the deri- was egter met 20 - 40 % ge-bhiier in vergelyking met die kontrole vatized product extracted with diethylether. The diethylether was studies. Heparin (plasmavlak = 2,S U/d) het nie 'n imrloed op PN &erred to a dean ampoule, evaporated to dryness, the residue gehad nie (p >0,02). In die studies waar die middel Iokaal toegedien dissolved in mobile phase and an aliquot injected onto the HPLC is, was PN met 82 % ge-dieer oor 'n 4-uur studieperiode (p~0.001, c o h Chromatography was performed in reverse phase mode on a n=5) dew behandeling met 13 mg/ml D-FPRCHzQ vir l5 minute. Lokale behandeGg met r-hirudin (30 mg/d) was nie effektief Bischoff, Spherisorb ODS E, 5p, 125x4.6mm column, and the nie analyte @>0,05; n=5). In kontrole studies waar die rostese vir 21 uur in die detected by fluorescence at exatation and emission wavelengths of permanente fistel gelaat is, het trombus-l' P In-aktiwiteit met 3 % 360M1 and 470nm respectively. toegeneem. Lokale behandeling van 'n 15 minuut-oue trombus met Rdts DFPRCH2Cl het trombus-l%-aktiwiteit met 46 % laat afneem in Caliiration curves were linear to at least 7lngIml with the hit of dieselfde tydperk. Dus, korttermyn, &IS min) lokale behandetkg quantification set at l.lng/ml The derhives we-re stable for at least van vormende trombi met DFPRCHzQ verminder of verhoed (vir 24 hours. >21 uur) opvolgende trombus-groei Sistemiese behandeling met r- hirudin en DFPRCHZQ vir 1 uur met konsentrasies wat stolling Condasion totaal inhieer (AF"IT>300 sekondes) het tot gevolg dat die trombus The procedure provided us with a sensitive and reliable method to wat tydens 4 urn gevom het, betekenisvol Heiner was as m koatrole determine low concentrations of maprotiline for 6 days in plasma after studies. a single 75mg oral dose of maprotiline.
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