Basic HTML Version
Molecular Microbiology Research (Online) 2012, Vol.2 No.1 1-9
ISSN 1027-5595
http://mmr.sophiapublisher.com
6
Quick release formulations for lactating animals
(Length of withdrawal period economic concern).
Slow release for dry cow treatment.
(2)
Pharmacokinetic phase
It includes absorption, distribution, metabolism,
excretion, which effects drug concentration in milk,
mammary tissue.
(3)
Pharmacodynaemic phase
①
Concentration-dependent killing
Magnitude above MIC enhances killing
Aminoglycosides, Floroquinolones
Peak serum > 10 times MIC
②
Time-dependent killing
Time above MIC, not peak concentration
Macrolids, Sulphonamide, Tetracycline, Penicillin
Cephalosporin, Lincosamides
(B)
Parentral Route
Highly lipophilic molecules pass through epithelia
such as Macrolids, Floroquinolones and Penethamate
hydroiodide (pro drug of Benzyl penicillin) are
suitable for systemic administration in mastitis.
Passage in both directions depends on the drug lipid
solubility and acid base properties. Normal milk is
acidic 6.5~6.9 than mastitic milk 6.9~7.5. So milk:
plasma concentration ratio is >1 for basic drugs and
<1 for acidic drugs. Lipophilic weak bases
erythromycin, lincomycin, spiramycin are easily
accessible in milk than benzyl penicillin, OTC,
dihydrostreptomycin.
(1) Ideal characteristics of antimicrobial agent
Low MIC.
High bioavailability.
Highly lipophilic.
High volume of distribution (Vd).
Macrolids are the best for gram positive infection.
Gentamicin, Polymyxin-B, Cephalosporins are the
best for gram-negative bacteria.
(2) Drugs In lactation period
Minimum irritation to udder.
Low MIC.
Low degree of binding to milk and udder proteins.
Low degree of ionization in udder.
Quick release rate from ointment or vehicle base.
Short milk withholding time.
(3) Dry period
Completely non irritation to udder.
Bactericidal action.
Slow release rate from base.
Large molecular weight.
Low volume of requirement of drug.
No withdrawal losses.
Treating udder in dry period is simply cost effective
way to manage pre-existing sub clinical infections and
prevent new ones from occurring (Hilson et al., 1986).
8 Clinical Pharmacology of Antimicrobial Use
in Mastitis
8.1 Striking pharmacokinetic features of different
antibiotics in mastitic milk
(A) Penicillins
In cow serum, normal milk and mastitic milk peak
ampicillin concentration are 5.2, 0.14, 0.28
respectively indicates two fold higher than that of
normal milk. This drug shows MIC against all types of
pathogens for 24 hrs at 20 mg/kg IM dose rate.
However amoxycillin=clavulenic acid @8.8 mg/kg
exhibits 0.6 µg/mL concentration is highly effective
(Table 4; Table 5) (Kartinnen et al., 1995).
Table 4 The disposition parameters in healthy and affected
Disposition parameters
Healthy
Affected
Cmax (µg.ml
-
1
)
0.8
0.25
Tmax (Min)
2.23
2.10
Cºp (µg.ml
-
1
)
0.90
0.40
T 1/2 (α) (Min)
18.90
19.90
T 1/2 (ß) (Min)
90.00
101.00
K 12 (Min
-
1
)
0.00692
0.00922
K 21 (Min
-1
)
0.02703
0.01656
Vd (area) (L.kg
-
1
)
5.5312
3.2312
ClB (ml/kg/min)
0.0494
0.00211