Yes, patients with Parkinson’s disease can become resistant to levodopa, either from the beginning of the onset or by developing reduced responsiveness over time. Resistance often happens as a result of disease progression, peripheral metabolic factors, or an misdiagnosis, such as atypical parkinsonism. Bacteria in the gut can prevent the metabolic breakdown of levodopa before it reaches the brain. Poor absorption or wrong dosage can also cause Levodopa not to be effective. My husband is on Ropinirole and low dose Tramadol for PD pain. Carbidopa levodopa caused problems for him too. Hopefully, you will find the right regimen for you. Remember, one pill doesn't always work for all!