Ph a r m a cok ine t ics I n t e r a ct ion of Glu cocor t icoids w it h
pr event ing phospholipid r elease and decreasing eosinophil act ion. To achieve an opt im um diagnost ic out com e, t his resear ch w as focused on phar m acokinet ics int er act ion and biodist r ibut ion vivo t han P- O- P bond of phosphat es. P- O- P bond can be easily broken down by phosphat ase enzym es, but t he P- C- P bond in diphosphonat e of 99mTc- MDP is not affect ed ( Khalil, 2011) . This com plexes were used for m et ast at ic bone cancer because t heir high sensit ivit y can det ect m et ast ases before occurrence of anat om ical changes ( Ogawa & I shizaki, 2015) ( Goyal & Ant onarakis, 2012) .Radiopharm aceut icals are used for t wo purposes. The first is t heir use as a t raced com pound adm inist ered t o a pat ient for observing physiological alt erat ions or abnorm al dist ribut ion t hroughout of t he body and t he second is t heir use as a t racer for biochem ical or physiological st udies ( Sant os-Oliveira, 2008) . The pharm acokinet ics or biodist ribut ion of radiopharm aceut ical m ay alt er by a variet y of drugs, disease st at es and surgical procedurs ( Sant os- Oliveira, 2008) , which a significant clinical im pact on safet y, scan int erpret at ion, and diagnost ic im aging accuracy ( Fact ors, 2010) .
M a t e r ia ls a n d M e t h ods
Radiolabeling of 99mTc- MDP and det erm inat ion of radiochem ical purit y ( Zolle, 2007)
The freeze- dried MDP kit was reconst it ut ed using 1 m L of freshly elut ed 99mTcO4solut ion cont aining 1 -accum ulat ion of each organ sam ples were calculat ed as percent age of inj ect ion dose per gram organ.
Re su lt s a n d D iscu ssion radiopharm aceut icals have been fulfilled t he requirem ent of Unit ed St at e of Pharm acopoeia, which t he percent age of radiochem ical purit y is great er t han 95% . The solut ion of MDP dissolved easily in saline, giving a clear and colorless solut ion, vacuum and pH bet ween 5.8 – 6.0.
The pharm acokinet ic profile was conduct ed t o det erm ine t he rat e of dist ribut ion and elim inat ion of 99mTc- MDP radiopharm aceut ical in t he body t hrough t he det erm inat ion of it s biological half life. As
A B
Figu r e 1 . The chrom at ogram of 99mTc- MDP using ( A) acet one as m obile phase and ( B) saline as m obile phase
About 12.34 and 12.06% of t he inj ect ed dose rem ains in t he blood at 1 hour post - inj ect ion and 0.19 and 0.18% at 24 hours, 99mTc- MDP were t reat m ent wit h dexam et hasone and prednisone. Following int ravenous adm inist rat ion, 99mTc- MDP is cleared from t he plasm a wit h a half- t im e of 3–4 m in. About 10% of t he inj ect ed dosage rem ains in t he blood at 1 hour post - inj ect ion and less t han 1% at 24 hours ( Saha, 2010) .
Figu r e 2 . Pharm acokinet ics profile of 99mTc- MDP using norm al m ice st ock swiss wit h t reat m ent of dexam et hasone and prednisone and wit hout t reat m ent as cont rol.
Based on calculat ions by t he m ult ifit soft ware ( Table 1) , it showed t hat t he dist ribut ion half- life of 99mTc- MDP wit h t reat m ent did not differ significant ly from cont rol. But t he elim inat ion half - life showed
a significant difference where t he biological half - life of 99mTc- MDP radiopharm aceut ical which t reat m ent wit h dexam et asone ( 4.61 h) and prednisone ( 4.43 h) , t he half- life m ore fast er t han cont rol ( 20.67 h) .
Ta ble 1 . Dist ribut ion and elim inat ion half- life of 99mTc- MDP radiopharm aceut ical given Glucocort icoids drug t reat m ent com pared t o cont rols wit hout t reat m ent using Mult ifit soft w are
t1/ 2dist ribut ion ( hours)
t1/ 2elim inat ion ( m inut es)
Cont rols ( wit hout t reat m ent ) 0.21 20.67
Treat m ent of Dexam et hasone 0.23 4.61
Treat m ent of Prednisone 0.20 4.43
Biodist ribut ion st udy was perform ed 3 hours aft er int ravenous inj ect ion of 99mTc- MDP t o anim al m odel. I n nuclear m edicine, im aging of bone scint igraphy using 99mTc- MDP usually perform ed 2 - 5 hours aft erwards for clearance of t he adm inist rat ed radiopharm aceut ical from t he int ravascular com part m ent and from t he ext racellular nonosseous soft t issues ( Zuckier & Mar t ineau, 2015) .
99mTc- MDP + 99mTcO
2 99mTc- MDP
+ 99mTcO 4
-99mTcO 2 99mTcO
-The adm inist rat ion of dexam et hasone and prednisone for several days has changed t he pat t ern of biodist ribut ion part icularly on t he bone. As show n in Figure 3, t he highest percent age shown in t he bone, but t he bones which given t reat m ent wit h dexam et hasone and prednisone reduced bone upt ake t han cont rol, result s were 3.5 3 ± 0.49 % and 3.47 ± 0.5% , respect ively which com pared t o t he cont rol 11.54 ± 4.36% ( t t est , differ significant ly wit h t he 95% confidence level) . Dexam et hasone and prednisone, glucocort icoids agent , are com m on t o cont rol and t reat several inflam m at ory diseases and side effect of t his agent s especially for long t erm is bone loss t hrough decrease qualit y and quant it y of m ineral bone densit y and rat e of ost eogenesis ( Doroudi et al., 2012) . A sm all am ount of bone synt hesis depends on decreased calcium availabilit y and decreased glucocort icoid - induced ost eoblast ic act ivit y ( Longui, 2007) . Based on t - t est , upt ake of non t arget organs showed t here are no significant ly differences bet ween t reat m ent s and cont rols. Non t arget organs have lower upt a ke t han bone ( t arget organ) , which are below t han 2.5% of inj ect ed dose per gram .
Figu r e 3 . Biodist ribut ion profile of 99mTc- MDP using norm al m ice st ock swiss wit h t reat m ent of dexam et hasone and prednisone and wit hout t reat m ent
Con clu sion s
Adm inist rat ion of dexam et hasone and prednisone as glucocort icoid agent can alt er pharm acokinet ics profile and biodist ribut ion pat t ern. Treat m ent of dexam et hasone and prednisone decreases bone upt ake and elim inat ion half- life of 99mTc- MDP radiopharm aceut icals
Ack n ow le dge m e n t s
The aut hor would like t o t hank t o Mr. I swahyudi, Achm ad Sidik, Epy I sabella and ot her colleagues who have helped in com plet ion of t his research.
Re fe re n ce s
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